1. Information
    majorVersion:3 minorVersion:0 projectID:local projectVersionID:undef fileName:/home/ikeda/eclipse/workspace/macrophage/csml/ok/csml/18226603.csml convertedTime:2009.07.01.11:14

  2. Original Literature
  3. Model OverView
  4. Model Abstracts
  5. Model Detail
  6. Download
Original Literature Model OverView
Publication
Title Silica binding and toxicity in alveolar macrophages.
Authors Hamilton RF Jr, Thakur SA, Holian A.
Affiliation Department of Biomedical and Pharmaceutical Sciences, Center for EnvironmentalHealth Sciences, University of Montana, 32 Campus Drive, SB 154, Missoula, MT59812, USA.
Abstract Inhalation of the crystalline form of silica is associated with a variety ofpathologies, from acute lung inflammation to silicosis, in addition toautoimmune disorders and cancer. Basic science investigators looking at themechanisms involved with the earliest initiators of disease are focused on howthe alveolar macrophage interacts with the inhaled silica particle and theconsequences of silica-induced toxicity on the cellular level. Based onexperimental results, several rationales have been developed for exactly howcrystalline silica particles are toxic to the macrophage cell that isfunctionally responsible for clearance of the foreign particle. For example,silica is capable of producing reactive oxygen species (ROS) either directly (onthe particle surface) or indirectly (produced by the cell as a response tosilica), triggering cell-signaling pathways initiating cytokine release andapoptosis. With murine macrophages, reactive nitrogen species are produced inthe initial respiratory burst in addition to ROS. An alternative explanation forsilica toxicity includes lysosomal permeability, by which silica disrupts thenormal internalization process leading to cytokine release and cell death. Stillother research has focused on the cell surface receptors (collectively known asscavenger receptors) involved in silica binding and internalization. Thesilica-induced cytokine release and apoptosis are described as the function ofreceptor-mediated signaling rather than free radical damage. Current researchideas on silica toxicity and binding in the alveolar macrophage are reviewed anddiscussed.
PMID 18226603
Model Abstract

Entity

G010329:TNF-alpha G010389:IL-1beta G010657:IL-12 p40 G010815:MCP1 G013287:MARCO MO000000011:ERK MO000000018:MEK MO000000022:p38 MO000000023:JNK MO000000058:NF-kappaB MO000000276:AP-1 {activated} MO000000289:TNF-alpha MO000000306:ICAM-1 MO000007321:IL-13 MO000008272:particle derived ROS MO000016597:IL-1beta MO000016665:IFNgamma MO000016797:phosphatidylinositide lipids MO000016882:LPS MO000016907:Caspases MO000016924:Caspase-3 MO000016987:Caspase-9 MO000017053:IL-4 MO000017065:PKCdelta MO000017264:IL-8 MO000017265:IL-12 MO000017280:MCP-1 MO000017824:A-SMase MO000021135:Hsp90 MO000021289:SOD MO000021614:Hsp70 MO000038305:MEK{p} MO000038306:ERK{p} MO000042355:MARCO MO000042963:cathepsin B MO000066361:GAPDH MO000081880:cathepsin D {extracellular} MO000101490:SR-A1 MO000107436:oxLDL e1: e10: e11:silica: SR-AII e12:silica: SR-A1 e13:silica: MERCO e14:Hsp90: MSR e15:Hosp70: MSR e16:MARCO: MARCO e17:titanium dioxide e18:titanium dioxide: SR-AII e19:titanium dioxide: SR-A1 e2: e20:titanium dioxide: MERCO e21:GAPDH: MSR e22:MSR e23:PKCdelta{p} e24:urokinase-type plasminogen activator e25:crocidolite asbestos e26:SR-A1{pS} e27:AP-1 e28:ac-LDL e29:ox-LDL: SR-A1 e3: e30:fucoidan: SR-A1 e31:fucoidan e32:cell-derived ROS e33:TLR4 ligand: TLR4 e34:RNS e35:peroxynitrite e36:hydroxyl radicals e37:hydrogen peroxide e38:nitric oxide e39:superoxide anion e4: e40:NF-kappaB {activated} e41:p38 {activated} e42:JNK {activated} e43:phosphatidylcholine-specific phospholipase C e44:phosphatidylcholine-specific phospholipase C {activated} e45:MIP-1 e46:MIP-1 e47:MIP-2 e48:MIP-2 e49:IL8 e5:SR-AII e50: e51: e52: e53: e54: e55: e56: e57: e58: e59: e6:silica e60: e61: e62: e63:dipalmitoyl lecithin e64:iron e65:ammonium chloride e66:surfactant protein e67:phospholipids e68:SP-A e69:SP-D e7: e70:vitamin E e71:phosphatidyl glycerol e72:2F-8 e73:2F-8: SR-A1 e74:Caspases {activated} e75:MnSOD e76:glutathione peroxidase e77:N-acetylcysteine e78:Caspase-3 {activated} e79:IFNgamma {intracellular} e8: e80:cathepsin D e81:A-SMase {activated} e82:Caspase-9{activated} e9:

Process

p1 p10 p11 p12 p13 p14 p15 p16 p17 p18 p19 p2 p20 p21 p22 p23 p24 p25 p26 p27 p28 p29 p3 p30 p31 p32 p33 p34 p35 p36 p37 p38 p39 p4 p40 p41 p42 p43 p44 p45 p46 p47 p48 p49 p5 p50 p51 p52 p53 p54 p55 p56 p57 p58 p59 p6 p60 p61 p62 p63 p64 p65 p66 p67 p68 p69 p7 p8 p9
Model Detail
442.0, 1127.0
28.0, 28.0

TNF-alpha

--

G010329

cso30:c:mRNA

cso30:i:CC_CellComponent

--

--

p41

true true true true

csml-variable:Double

m93309

10

false

infinite

0

unit false false false
TRANSFACG010329

--

Go back
441.0, 1170.0
30.0, 30.0

IL-1beta

--

G010389

cso30:c:mRNA

cso30:i:CC_CellComponent

--

--

p42

true true true true

csml-variable:Double

m93364

10

false

infinite

0

unit false false false
TRANSFACG010389

--

Go back
736.0, 1164.0
32.0, 32.0

IL-12 p40

--

G010657

cso30:c:mRNA

cso30:i:CC_CellComponent

--

p19 p20

p21

true true true true

csml-variable:Double

m93589

10

false

infinite

0

unit false false false
TRANSFACG010657

--

Go back
696.0, 1272.0
24.0, 24.0

MCP1

--

G010815

cso30:c:mRNA

cso30:i:CC_Nucleoplasm

--

--

p45

true true true true

csml-variable:Double

m93710

10

false

infinite

0

unit false false false
TRANSFACG010815

--

Go back
524.0, 1221.0
31.0, 31.0

MARCO

--

G013287

cso30:c:mRNA

cso30:i:CC_CellComponent

--

p18

--

true true true true

csml-variable:Double

m95765

10

false

infinite

0

unit false false false
TRANSFACG013287

--

Go back
369.0, 638.0
30.0, 30.0

ERK

--

MO000000011

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p36

true true true true

csml-variable:Double

m42

10

false

infinite

0

unit false false false
TRANSPATHMO000000011

--

Go back
537.0, 594.0
30.0, 30.0

MEK

--

MO000000018

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p35

true true true true

csml-variable:Double

m41

10

false

infinite

0

unit false false false
TRANSPATHMO000000018

--

Go back
468.0, 829.0
23.0, 23.0

p38

--

MO000000022

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p37

true true true true

csml-variable:Double

m43

10

false

infinite

0

unit false false false
TRANSPATHMO000000022

--

Go back
378.0, 703.0
28.0, 28.0

JNK

--

MO000000023

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p39

true true true true

csml-variable:Double

m45

10

false

infinite

0

unit false false false
TRANSPATHMO000000023

--

Go back
470.0, 1019.0
28.0, 28.0

NF-kappaB

--

MO000000058

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p34

true true true true

csml-variable:Double

m40

10

false

infinite

0

unit false false false
TRANSPATHMO000000058

--

Go back
579.0, 1096.0
26.0, 26.0

AP-1 {activated}

--

MO000000276

cso30:c:Protein

cso30:i:CC_CellComponent

--

p38

--

true true true true

csml-variable:Double

m219

10

false

infinite

0

unit false false false
TRANSPATHMO000000276

--

Go back
169.0, 1126.0
30.0, 30.0

TNF-alpha

--

MO000000289

cso30:c:Protein

cso30:i:CC_CellComponent

--

p41

--

true true true true

csml-variable:Double

m230

10

false

infinite

0

unit false false false
InterProIPR003636
TRANSPATHMO000000289

--

Go back
972.0, 373.0
32.0, 32.0

ICAM-1

--

MO000000306

cso30:c:Protein

cso30:i:CC_CellComponent

--

p22

--

true true true true

csml-variable:Double

m242

10

false

infinite

0

unit false false false
InterProIPR003987
TRANSPATHMO000000306

--

Go back
603.0, 708.0
26.0, 26.0

IL-13

--

MO000007321

cso30:c:Protein

cso30:i:CC_CellComponent

--

p62

--

true true true true

csml-variable:Double

m836

10

false

infinite

0

unit false false false
InterProIPR001325
TRANSPATHMO000007321

--

Go back
885.0, 338.0
30.0, 30.0

particle derived ROS

--

MO000008272

cso30:c:Protein

cso30:i:CC_CellComponent

--

p23

p26 p30 p32

true true true true

csml-variable:Double

m1063

10

false

infinite

0

unit false false false
TRANSPATHMO000008272

--

Go back
170.0, 1171.0
28.0, 28.0

IL-1beta

--

MO000016597

cso30:c:Protein

cso30:i:CC_CellComponent

--

p42

--

true true true true

csml-variable:Double

m1591

10

false

infinite

0

unit false false false
TRANSPATHMO000016597

--

Go back
1200.0, 1177.0
32.0, 32.0

IFNgamma

--

MO000016665

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p20

true true true true

csml-variable:Double

m1639

10

false

infinite

0

unit false false false
InterProIPR002069
TRANSPATHMO000016665

--

Go back
887.0, 868.0
26.0, 26.0

phosphatidylinositide lipids

--

MO000016797

cso30:c:Protein

cso30:i:CC_CellComponent

--

p54

--

true true true true

csml-variable:Double

m1736

10

false

infinite

0

unit false false false
TRANSPATHMO000016797

--

Go back
1201.0, 1134.0
30.0, 30.0

LPS

--

MO000016882

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p19

true true true true

csml-variable:Double

m155666

10

false

infinite

0

unit false false false
TRANSPATHMO000016882

--

Go back
377.0, 334.0
30.0, 30.0

Caspases

--

MO000016907

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p57

true true true true

csml-variable:Double

m1822

10

false

infinite

0

unit false false false
TRANSPATHMO000016907

--

Go back
392.0, 1269.0
32.0, 32.0

Caspase-3

--

MO000016924

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p67

true true true true

csml-variable:Double

m1839

10

false

infinite

0

unit false false false
TRANSPATHMO000016924

--

Go back
509.0, 1334.0
30.0, 30.0

Caspase-9

--

MO000016987

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p68

true true true true

csml-variable:Double

m1891

10

false

infinite

0

unit false false false
TRANSPATHMO000016987

--

Go back
650.0, 839.0
22.0, 22.0

IL-4

--

MO000017053

cso30:c:Protein

cso30:i:CC_CellComponent

--

p64

--

true true true true

csml-variable:Double

m1947

10

false

infinite

0

unit false false false
InterProIPR001325
TRANSPATHMO000017053

--

Go back
413.0, 534.0
30.5, 30.5

PKCdelta

--

MO000017065

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p11 p13

true true true true

csml-variable:Double

m1957

10

false

infinite

0

unit false false false
InterProIPR000719
TRANSPATHMO000017065

--

Go back
1118.0, 1347.0
28.0, 28.0

IL-8

--

MO000017264

cso30:c:Protein

cso30:i:CC_CellComponent

--

p46

--

true true true true

csml-variable:Double

m2120

10

false

infinite

0

unit false false false
InterProIPR002473
TRANSPATHMO000017264

--

Go back
966.0, 1107.0
28.0, 28.0

IL-12

--

MO000017265

cso30:c:Protein

cso30:i:CC_CellComponent

--

p21

--

true true true true

csml-variable:Double

m2121

10

false

infinite

0

unit false false false
TRANSPATHMO000017265

--

Go back
1114.0, 1303.0
28.0, 28.0

MCP-1

--

MO000017280

cso30:c:Protein

cso30:i:CC_CellComponent

--

p45

--

true true true true

csml-variable:Double

m2133

10

false

infinite

0

unit false false false
InterProIPR008097
TRANSPATHMO000017280

--

Go back
322.0, 1307.0
28.0, 28.0

A-SMase

--

MO000017824

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p66

true true true true

csml-variable:Double

m2576

10

false

infinite

0

unit false false false
InterProIPR008139
TRANSPATHMO000017824

--

Go back
98.0, 671.0
36.0, 36.0

Hsp90

--

MO000021135

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p8

true true true true

csml-variable:Double

m5516

10

false

infinite

0

unit false false false
TRANSPATHMO000021135

--

Go back
649.0, 786.0
22.0, 22.0

SOD

--

MO000021289

cso30:c:Protein

cso30:i:CC_CellComponent

--

p59

--

true true true true

csml-variable:Double

m5655

10

false

infinite

0

unit false false false
TRANSPATHMO000021289

--

Go back
102.0, 719.0
28.0, 28.0

Hsp70

--

MO000021614

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p9

true true true true

csml-variable:Double

m5956

10

false

infinite

0

unit false false false
InterProIPR001023
TRANSPATHMO000021614

--

Go back
520.0, 645.0
31.0, 31.0

MEK{p}

--

MO000038305

cso30:c:Protein

cso30:i:CC_CellComponent

--

p35

p39

true true true true

csml-variable:Double

m16521

10

false

infinite

0

unit false false false
TRANSPATHMO000038305

--

Go back
499.0, 752.0
34.0, 34.0

ERK{p}

--

MO000038306

cso30:c:Protein

cso30:i:CC_CellComponent

--

p36

p37

true true true true

csml-variable:Double

m16522

10

false

infinite

0

unit false false false
TRANSPATHMO000038306

--

Go back
803.0, 245.0
26.0, 26.0

MARCO

--

MO000042355

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p4 p7

true true true true

csml-variable:Double

m20155

10

false

infinite

0

unit false false false
TRANSPATHMO000042355

--

Go back
468.0, 345.0
24.0, 24.0

cathepsin B

--

MO000042963

cso30:c:Protein

cso30:i:CC_CellComponent

--

p47 p48

--

true true true true

csml-variable:Double

m20747

10

false

infinite

0

unit false false false
TRANSPATHMO000042963

--

Go back
105.0, 774.0
27.0, 27.0

GAPDH

--

MO000066361

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p10

true true true true

csml-variable:Double

m41219

10

false

infinite

0

unit false false false
TRANSPATHMO000066361

--

Go back
171.0, 1252.0
26.0, 26.0

cathepsin D {extracellular}

--

MO000081880

cso30:c:Protein

cso30:i:CC_CellComponent

--

p65

--

true true true true

csml-variable:Double

m56148

10

false

infinite

0

unit false false false
TRANSPATHMO000081880

--

Go back
640.0, 234.0
32.0, 32.0

SR-A1

--

MO000101490

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p2 p6 p15 p16 p17 p56

true true true true

csml-variable:Double

m74475

10

false

infinite

0

unit false false false
TRANSPATHMO000101490

--

Go back
118.0, 425.0
28.0, 28.0

oxLDL

--

MO000107436

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p16

true true true true

csml-variable:Double

m341431

10

false

infinite

0

unit false false false
TRANSPATHMO000107436

--

Go back
230.75, 213.9969080091176
856.2594311764528, 1243.2886940682085

--

e1

cso30:c:EntityBiologicalCompartment

cso30:i:CC_PlasmaMembrane

--

--

--

true true true true

csml-variable:Double

m1

0

false

infinite

0

unit false true false

--

Go back
239.0, 233.0
829.9775981223105, 1167.545103664102

--

e10

cso30:c:EntityBiologicalCompartment

cso30:i:CC_Cytosol

--

--

--

true true true true

csml-variable:Double

m10

0

false

infinite

0

unit false true false

--

Go back
471.625, 229.5
33.467547075487424, 40.98066988835194

silica: SR-AII

--

e11

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

p1

--

true true true true

csml-variable:Double

m11

0

false

infinite

0

unit false false false

--

Go back
716.625, 227.5
30.029953341109813, 36.77137143809365

silica: SR-A1

--

e12

cso30:c:Complex

cso30:i:CC_Cytosol

--

p2

p11 p19 p20 p21 p23 p24 p25 p26 p27 p28 p29 p40 p43 p44 p45 p46 p47 p48 p49 p50 p51 p52 p53 p54 p55 p59 p60 p61 p62 p63 p64 p65 p66 p67 p68

true true true true

csml-variable:Double

m12

0

false

infinite

0

unit false false false

--

Go back
927.625, 229.5
32.87964505915681, 40.260789868355275

silica: MERCO

--

e13

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_InternalSideOfPlasmaMembrane_

--

p3

p19 p21 p58

true true true true

csml-variable:Double

m13

0

false

infinite

0

unit false false false

--

Go back
247.625, 629.5
32.03861856357273, 39.230961506415596

Hsp90: MSR

--

e14

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

p8

--

true true true true

csml-variable:Double

m14

0

false

infinite

0

unit false false false

--

Go back
247.625, 713.5
32.03861856357273, 39.230961506415596

Hosp70: MSR

--

e15

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

p9

--

true true true true

csml-variable:Double

m15

0

false

infinite

0

unit false false false

--

Go back
867.5, 236.125
41.32, 30.99

MARCO: MARCO

--

e16

cso30:c:Protein

cso30:i:CC_Cytosol

--

p4

p3

true true true true

csml-variable:Double

m16

0

false

infinite

0

unit false false false

--

Go back
513.5, 93.25
37.78385197645079, 21.41084945332212

titanium dioxide

--

e17

cso30:c:SmallMolecule

cso30:i:CC_Extracellular

--

--

p5 p6 p7

true true true true

csml-variable:Double

m17

0

false

infinite

0

unit false false false

--

Go back
388.625, 231.5
29.8993084485919, 36.61139810031661

titanium dioxide: SR-AII

--

e18

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

p5

--

true true true true

csml-variable:Double

m18

0

false

infinite

0

unit false false false

--

Go back
583.625, 213.5
33.639018496917174, 41.1906348941843

titanium dioxide: SR-A1

--

e19

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

p6

--

true true true true

csml-variable:Double

m19

0

false

infinite

0

unit false false false

--

Go back
230.75, 213.9969080091176
856.2594311764528, 1243.2886940682085

--

e2

cso30:c:EntityBiologicalCompartment

cso30:i:CC_PlasmaMembrane_ExternalSideOfPlasmaMembrane_

--

--

--

true true true true

csml-variable:Double

m2

0

false

infinite

0

unit false true false

--

Go back
975.625, 217.5
32.920471588068644, 40.310781536410595

titanium dioxide: MERCO

--

e20

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_InternalSideOfPlasmaMembrane_

--

p7

--

true true true true

csml-variable:Double

m20

0

false

infinite

0

unit false false false

--

Go back
245.625, 766.5
34.88831028161973, 42.72037993667722

GAPDH: MSR

--

e21

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

p10

--

true true true true

csml-variable:Double

m21

0

false

infinite

0

unit false false false

--

Go back
250.0, 675.0
28.0, 28.0

MSR

--

e22

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p8 p9 p10

true true true true

csml-variable:Double

m22

10

false

infinite

0

unit false false false
Affymetrix208422_at
EnsemblENSG00000038945
HGNCMSR1
InterProIPR003543
OMIM153622
PIRA38415
PROSITEPS00420
ProteomeHumanPSD/MSR1
RefSeqNM_002445
TRANSPATHMO000116148
UnigeneHs.147635
UniProtP21757

--

Go back
411.0, 576.0
32.0, 32.0

PKCdelta{p}

--

e23

cso30:c:Protein

cso30:i:CC_CellComponent

--

p11 p13

p12 p14 p35 p36 p34

true true true true

csml-variable:Double

m23

10

false

infinite

0

unit false false false
TRANSPATHMO000048712

--

Go back
476.0, 1086.0
39.75778546712802, 21.204152249134946

urokinase-type plasminogen activator

--

e24

cso30:c:mRNA

cso30:i:CC_Nucleoplasm

--

p12

--

true true true true

csml-variable:Double

m24

0

false

infinite

0

unit false false false

--

Go back
161.5, 554.25
34.85702270815811, 19.752312867956267

crocidolite asbestos

--

e25

cso30:c:SmallMolecule

cso30:i:CC_Extracellular

--

--

p13

true true true true

csml-variable:Double

m25

0

false

infinite

0

unit false false false

--

Go back
339.5, 246.125
32.84, 24.63

SR-A1{pS}

--

e26

cso30:c:Protein

cso30:i:CC_Cytosol

--

p15

--

true true true true

csml-variable:Double

m26

0

false

infinite

0

unit false false false

--

Go back
611.0, 1044.0
26.0, 26.0

AP-1

--

e27

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p38

true true true true

csml-variable:Double

m27

10

false

infinite

0

unit false false false
TRANSPATHMO000000276

--

Go back
167.0, 276.0
34.0, 34.0

ac-LDL

--

e28

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p15

true true true true

csml-variable:Double

m28

10

false

infinite

0

unit false false false
TRANSPATHMO000000290

--

Go back
255.625, 462.5
24.600024995834026, 30.12247958673554

ox-LDL: SR-A1

--

e29

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

p16

--

true true true true

csml-variable:Double

m29

0

false

infinite

0

unit false false false

--

Go back
247.87518862352903, 231.12209663264667
822.0090539293948, 1209.0383168211513

--

e3

cso30:c:EntityBiologicalCompartment

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

--

--

true true true true

csml-variable:Double

m3

0

false

infinite

0

unit false true false

--

Go back
255.625, 510.5
24.787827028828534, 30.35244125979003

fucoidan: SR-A1

--

e30

cso30:c:Complex

cso30:i:CC_Cytosol

--

p17

--

true true true true

csml-variable:Double

m30

0

false

infinite

0

unit false false false

--

Go back
112.5, 486.25
38.08662741799832, 21.582422203532378

fucoidan

--

e31

cso30:c:SmallMolecule

cso30:i:CC_Extracellular

--

--

p17

true true true true

csml-variable:Double

m31

0

false

infinite

0

unit false false false

--

Go back
885.0, 382.0
30.0, 30.0

cell-derived ROS

--

e32

cso30:c:Protein

cso30:i:CC_CellComponent

--

p24

p26 p33 p31

true true true true

csml-variable:Double

m32

10

false

infinite

0

unit false false false
TRANSPATHMO000008272

--

Go back
252.625, 1218.5
30.87914514247625, 37.81119813364439

TLR4 ligand: TLR4

--

e33

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

--

p18

true true true true

csml-variable:Double

m33

0

false

infinite

0

unit false false false

--

Go back
887.5, 436.25
32.031118587047935, 18.150967199327162

RNS

--

e34

cso30:c:SmallMolecule

cso30:i:CC_Cytosol

--

p25

--

true true true true

csml-variable:Double

m34

0

false

infinite

0

unit false false false

--

Go back
884.5, 482.25
39.70142977291842, 22.497476871320433

peroxynitrite

--

e35

cso30:c:SmallMolecule

cso30:i:CC_Cytosol

--

p26

--

true true true true

csml-variable:Double

m35

0

false

infinite

0

unit false false false

--

Go back
887.5, 625.25
41.54331370899916, 23.541211101766187

hydroxyl radicals

--

e36

cso30:c:SmallMolecule

cso30:i:CC_Cytosol

--

p29

--

true true true true

csml-variable:Double

m36

0

false

infinite

0

unit false false false

--

Go back
887.5, 577.25
41.34146341463414, 23.426829268292682

hydrogen peroxide

--

e37

cso30:c:SmallMolecule

cso30:i:CC_Cytosol

--

p28

--

true true true true

csml-variable:Double

m37

0

false

infinite

0

unit false false false

--

Go back
965.5, 442.25
37.78385197645079, 21.41084945332212

nitric oxide

--

e38

cso30:c:SmallMolecule

cso30:i:CC_Cytosol

--

--

p26

true true true true

csml-variable:Double

m38

0

false

infinite

0

unit false false false

--

Go back
883.5, 525.25
41.54331370899916, 23.541211101766187

superoxide anion

--

e39

cso30:c:SmallMolecule

cso30:i:CC_Cytosol

--

p27

p26

true true true true

csml-variable:Double

m39

0

false

infinite

0

unit false false false

--

Go back
279.5567875770579, 261.09117672382234
758.6458560223374, 1149.1001566387988

--

e4

cso30:c:EntityBiologicalCompartment

cso30:i:CC_PlasmaMembrane_InternalSideOfPlasmaMembrane_

--

--

--

true true true true

csml-variable:Double

m4

0

false

infinite

0

unit false true false

--

Go back
518.0, 1051.0
28.0, 28.0

NF-kappaB {activated}

--

e40

cso30:c:Protein

cso30:i:CC_CellComponent

--

p34

p42 p41

true true true true

csml-variable:Double

m47

10

false

infinite

0

unit false false false
TRANSPATHMO000000058

--

Go back
528.0, 897.0
24.0, 24.0

p38 {activated}

--

e41

cso30:c:Protein

cso30:i:CC_CellComponent

--

p37

p38

true true true true

csml-variable:Double

m44

10

false

infinite

0

unit false false false
TRANSPATHMO000000022

--

Go back
562.0, 807.0
28.0, 28.0

JNK {activated}

--

e42

cso30:c:Protein

cso30:i:CC_CellComponent

--

p39

p38

true true true true

csml-variable:Double

m46

10

false

infinite

0

unit false false false
TRANSPATHMO000000023

--

Go back
336.5, 835.125
31.838398068021743, 19.633678808613404

phosphatidylcholine-specific phospholipase C

--

e43

cso30:c:Protein

cso30:i:CC_Cytosol

--

--

p40

true true true true

csml-variable:Double

m48

0

false

infinite

0

unit false false false

--

Go back
336.5, 890.125
31.838398068021743, 19.633678808613404

phosphatidylcholine-specific phospholipase C {activated}

--

e44

cso30:c:Protein

cso30:i:CC_Cytosol

--

p40

p42 p41

true true true true

csml-variable:Double

m49

0

false

infinite

0

unit false false false

--

Go back
778.0, 1219.0
28.0, 28.0

MIP-1

--

e45

cso30:c:mRNA

cso30:i:CC_Nucleoplasm

--

--

p43

true true true true

csml-variable:Double

m63

10

false

infinite

0

unit false false false
Affymetrix102424_at
EnsemblENSMUSG00000000982
MGDCcl3
ProteomeHumanPSD/Ccl3
RefSeqNM_011337
TRANSFACG001238
UnigeneMm.1282

--

Go back
1114.0, 1219.0
28.0, 28.0

MIP-1

--

e46

cso30:c:Protein

cso30:i:CC_CellComponent

--

p43

--

true true true true

csml-variable:Double

m64

10

false

infinite

0

unit false false false
InterProIPR000827
TRANSPATHMO000019886

--

Go back
750.5, 1264.0
35.29411764705883, 18.823529411764707

MIP-2

--

e47

cso30:c:mRNA

cso30:i:CC_Nucleolus

--

--

p44

true true true true

csml-variable:Double

m65

0

false

infinite

0

unit false false false

--

Go back
1108.5, 1261.125
39.264439525055344, 24.213071040450796

MIP-2

--

e48

cso30:c:Protein

cso30:i:CC_Extracellular

--

p44

--

true true true true

csml-variable:Double

m66

0

false

infinite

0

unit false false false

--

Go back
646.0, 1286.0
28.0, 28.0

IL8

--

e49

cso30:c:mRNA

cso30:i:CC_Nucleoplasm

--

--

p46

true true true true

csml-variable:Double

m67

10

false

infinite

0

unit false false false
Affymetrix1369_s_at
EnsemblENSG00000169429
HGNCIL8
OMIM146930
ProteomeHumanPSD/IL8
RefSeqNM_000584
TRANSFACG000317
UnigeneHs.551925

--

Go back
517.375, 223.5
29.25, 45.0

SR-AII

--

e5

cso30:c:Protein

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

p1

p5

true true true true

csml-variable:Double

m5

0

false

infinite

0

unit false false false

--

Go back
412.0, 931.0
465.6500709748862, 422.29345356567933

--

e50

cso30:c:EntityBiologicalCompartment

cso30:i:CC_NuclearEnvelopeLumen

--

--

--

true true true true

csml-variable:Double

m50

0

false

infinite

0

unit false true false

--

Go back
462.29367619468036, 941.0077409313898
272.27955732982184, 409.2864683429171

--

e51

cso30:c:EntityBiologicalCompartment

cso30:i:CC_NuclearPore

--

--

--

true true true true

csml-variable:Double

m51

0

false

infinite

0

unit false true false

--

Go back
418.06992643728904, 936.6363602631969
453.51021810030846, 411.0207330392853

--

e52

cso30:c:EntityBiologicalCompartment

cso30:i:CC_NuclearInnerMembrane

--

--

--

true true true true

csml-variable:Double

m52

0

false

infinite

0

unit false true false

--

Go back
418.93705878547314, 937.503492611381
451.7759534039399, 409.2864683429171

--

e53

cso30:c:EntityBiologicalCompartment

cso30:i:CC_NuclearLumen

--

--

--

true true true true

csml-variable:Double

m53

0

false

infinite

0

unit false true false

--

Go back
412.0, 931.0
465.6500709748862, 422.29345356567933

--

e54

cso30:c:EntityBiologicalCompartment

cso30:i:CC_NuclearOuterMembrane

--

--

--

true true true true

csml-variable:Double

m54

0

false

infinite

0

unit false true false

--

Go back
412.0, 931.0
465.6500709748862, 422.29345356567933

--

e55

cso30:c:EntityBiologicalCompartment

cso30:i:CC_Nucleus

--

--

--

true true true true

csml-variable:Double

m55

0

false

infinite

0

unit false true false

--

Go back
418.93705878547314, 937.503492611381
451.7759534039399, 409.2864683429171

--

e56

cso30:c:EntityBiologicalCompartment

cso30:i:CC_Nucleoplasm

--

--

--

true true true true

csml-variable:Double

m56

0

false

infinite

0

unit false true false

--

Go back
751.9158804881849, 1104.426469636829
29.091257918298922, 26.33524401024959

--

e57

cso30:c:EntityBiologicalCompartment

cso30:i:CC_NuclearBody

--

--

--

true true true true

csml-variable:Double

m57

0

false

infinite

0

unit false true false

--

Go back
675.6082338479803, 1225.8249983826097
82.37757307749382, 74.57338194383664

--

e58

cso30:c:EntityBiologicalCompartment

cso30:i:CC_Nucleolus

--

--

--

true true true true

csml-variable:Double

m58

0

false

infinite

0

unit false true false

--

Go back
412.0, 931.0
465.6500709748862, 422.29345356567933

--

e59

cso30:c:EntityBiologicalCompartment

cso30:i:CC_NuclearEnvelope

--

--

--

true true true true

csml-variable:Double

m59

0

false

infinite

0

unit false true false

--

Go back
632.0, 114.5
47.14011516314779, 25.927063339731284

silica

--

e6

cso30:c:SmallMolecule

cso30:i:CC_Extracellular

--

--

p1 p2 p3 p22

true true true true

csml-variable:Double

m6

0

false

infinite

0

unit false false false

--

Go back
521.7511016961721, 1118.6637213250547
14.746453546866459, 7.100144300343119

--

e60

cso30:c:EntityBiologicalCompartment

cso30:i:CC_Chromatin

--

--

--

true true true true

csml-variable:Double

m60

0

false

infinite

0

unit false true false

--

Go back
521.2586758712023, 1097.489410851356
50.4736470593979, 90.85256470691624

--

e61

cso30:c:EntityBiologicalCompartment

cso30:i:CC_NuclearChromosome

--

--

--

true true true true

csml-variable:Double

m61

0

false

infinite

0

unit false true false

--

Go back
542.4329863449013, 1156.5805098477247
7.878813199515761, 7.8788131995157675

--

e62

cso30:c:EntityBiologicalCompartment

cso30:i:CC_NuclearCentromere

--

--

--

true true true true

csml-variable:Double

m62

0

false

infinite

0

unit false true false

--

Go back
579.6804037005887, 318.0
40.31959629941127, 22.84777123633305

dipalmitoyl lecithin

--

e63

cso30:c:SmallMolecule

cso30:i:CC_Cytosol

--

--

p47

true true true true

csml-variable:Double

m68

0

false

infinite

0

unit false false false

--

Go back
967.5, 580.0
25.47140234430166, 25.903121028103378

iron

--

e64

cso30:c:SmallMolecule

cso30:i:CC_Cytosol

--

--

p29

true true true true

csml-variable:Double

m69

0

false

infinite

0

unit false false false

--

Go back
515.0, 437.0
42.26240538267451, 23.948696383515557

ammonium chloride

--

e65

cso30:c:SmallMolecule

cso30:i:CC_Cytosol

--

--

p48

true true true true

csml-variable:Double

m70

0

false

infinite

0

unit false false false

--

Go back
889.5, 672.125
29.894344938619444, 18.43484604548199

surfactant protein

--

e66

cso30:c:Protein

cso30:i:CC_Cytosol

--

p49

--

true true true true

csml-variable:Double

m71

0

false

infinite

0

unit false false false

--

Go back
886.5, 707.25
34.730866274179974, 19.680824222035323

phospholipids

--

e67

cso30:c:SmallMolecule

cso30:i:CC_Cytosol

--

p50

--

true true true true

csml-variable:Double

m72

0

false

infinite

0

unit false false false

--

Go back
887.5, 747.125
32.29724290601732, 19.91663312537734

SP-A

--

e68

cso30:c:Protein

cso30:i:CC_Cytosol

--

p51

--

true true true true

csml-variable:Double

m73

0

false

infinite

0

unit false false false

--

Go back
888.5, 791.125
31.790098611390626, 19.603894143690887

SP-D

--

e69

cso30:c:Protein

cso30:i:CC_Cytosol

--

p52

--

true true true true

csml-variable:Double

m74

0

false

infinite

0

unit false false false

--

Go back
242.0, 219.0
839.7237354966342, 1189.8668429177399

--

e7

cso30:c:EntityBiologicalCompartment

cso30:i:CC_Cell

--

--

--

true true true true

csml-variable:Double

m7

0

false

infinite

0

unit false true false

--

Go back
881.5, 830.25
36.67367535744323, 20.781749369217827

vitamin E

--

e70

cso30:c:SmallMolecule

cso30:i:CC_Cytosol

--

p53

--

true true true true

csml-variable:Double

m75

0

false

infinite

0

unit false false false

--

Go back
881.5, 906.25
37.026913372582, 20.98191757779647

phosphatidyl glycerol

--

e71

cso30:c:SmallMolecule

cso30:i:CC_Cytosol

--

p55

--

true true true true

csml-variable:Double

m76

0

false

infinite

0

unit false false false

--

Go back
117.0, 291.5
22.769230769230766, 34.15384615384616

2F-8

--

e72

cso30:c:Protein

cso30:i:CC_Extracellular

--

--

p56

true true true true

csml-variable:Double

m77

0

false

infinite

0

unit false false false

--

Go back
251.625, 329.5
25.220588235294116, 30.882352941176467

2F-8: SR-A1

--

e73

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

p56

p57

true true true true

csml-variable:Double

m78

0

false

infinite

0

unit false false false

--

Go back
381.0, 370.0
30.0, 30.0

Caspases {activated}

--

e74

cso30:c:Protein

cso30:i:CC_CellComponent

--

p57

--

true true true true

csml-variable:Double

m79

10

false

infinite

0

unit false false false
TRANSPATHMO000016907

--

Go back
620.5, 743.125
31.89877238881063, 19.670909639766553

MnSOD

--

e75

cso30:c:Protein

cso30:i:CC_Cytosol

--

p61

--

true true true true

csml-variable:Double

m80

0

false

infinite

0

unit false false false

--

Go back
715.5, 1128.0
33.99653979238755, 18.13148788927336

glutathione peroxidase

--

e76

cso30:c:mRNA

cso30:i:CC_Nucleoplasm

--

p60

--

true true true true

csml-variable:Double

m81

0

false

infinite

0

unit false false false

--

Go back
1206.5, 675.25
34.85702270815811, 19.752312867956267

N-acetylcysteine

--

e77

cso30:c:SmallMolecule

cso30:i:CC_Cytosol

--

--

p23 p24 p30 p31

true true true true

csml-variable:Double

m82

0

false

infinite

0

unit false false false

--

Go back
428.0, 1329.0
32.0, 32.0

Caspase-3 {activated}

--

e78

cso30:c:Protein

cso30:i:CC_CellComponent

--

p67

p69

true true true true

csml-variable:Double

m83

10

false

infinite

0

unit false false false
TRANSPATHMO000016924

--

Go back
605.0, 670.0
22.0, 22.0

IFNgamma {intracellular}

--

e79

cso30:c:Protein

cso30:i:CC_CellComponent

--

p63

--

true true true true

csml-variable:Double

m84

10

false

infinite

0

unit false false false
InterProIPR002069
TRANSPATHMO000016665

--

Go back
245.0, 240.0
805.5569854171277, 1169.6687428256696

--

e8

cso30:c:EntityBiologicalCompartment

cso30:i:CC_Cell_WithoutCellWall_

--

--

--

true true true true

csml-variable:Double

m8

0

false

infinite

0

unit false true false

--

Go back
327.0, 1272.0
26.0, 26.0

cathepsin D

--

e80

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p65

true true true true

csml-variable:Double

m85

10

false

infinite

0

unit false false false
TRANSPATHMO000081880

--

Go back
319.0, 1348.0
26.0, 26.0

A-SMase {activated}

--

e81

cso30:c:Protein

cso30:i:CC_CellComponent

--

p66

--

true true true true

csml-variable:Double

m86

10

false

infinite

0

unit false false false
InterProIPR008139
TRANSPATHMO000017824

--

Go back
585.0, 1362.0
30.0, 30.0

Caspase-9{activated}

--

e82

cso30:c:Protein

cso30:i:CC_CellComponent

--

p68

p69

true true true true

csml-variable:Double

m87

10

false

infinite

0

unit false false false
TRANSPATHMO000016987

--

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253.0, 261.0
801.8791759029863, 1154.3288303559784

--

e9

cso30:c:EntityBiologicalCompartment

cso30:i:CC_Cytoplasm

--

--

--

true true true true

csml-variable:Double

m9

0

false

infinite

0

unit false true false

--

Go back
518.0, 160.0
27.5, 27.5

p1

p1

cso30:i:ME_Binding

cso30:i:CC_Extracellular

--

e6

e11 e5

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c1 : 1
stoichiometry:c3 : 1
stoichiometry:c2 : 1

m6*0.1

nodelay

--

true

0

false

PMID: 18226603, 11899233, 7541421 The SR most associated with AM silica binding are SR-AI, SR-AII, and MARCO.

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166.0, 775.0
25.0, 25.0

p10

p10

cso30:i:ME_Binding

cso30:i:CC_Extracellular

--

MO000066361 e22

e21

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c23 : 1
stoichiometry:c28 : 1
stoichiometry:c29 : 1

m41219*m22*0.1

nodelay

--

true

0

false

PMID: 18226603, 11785981 One study, using a synthetic bovine SR-A construct, demonstrated that heat-shock proteins HSP90 and HSP70, in addition to glyceraldehyde-3-phosphate dehydrogenase, bound to the cytoplasmic N-terminus of the SR.

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486.0, 547.0
25.0, 25.0

p11

p11

cso30:i:ME_Phosphorylation

cso30:i:CC_Cytosol

--

e12 MO000017065

e23

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c30 : 1
stoichiometry:c31 : 1
stoichiometry:c32 : 1

m12*m1957*0.1

nodelay

--

true

0

false

PMID: 18226603, 9422792 Hsu et al. found that SR-A ligand-induced tyrosine phosphorylation followed by activation of protein kinase C (PKC) resulted in urokinase-type plasminogen activator expression in THP-1 cells.

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432.0, 1085.0
23.0, 23.0

p12

p12

cso30:i:ME_GeneExpression

cso30:i:CC_Nucleoplasm

--

e23

e24

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c33 : 1
stoichiometry:c34 : 1

m23*0.1

nodelay

--

true

0

false

PMID: 18226603, 9422792 Hsu et al. found that SR-A ligand-induced tyrosine phosphorylation followed by activation of protein kinase C (PKC) resulted in urokinase-type plasminogen activator expression in THP-1 cells.

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321.0, 550.0
27.0, 27.0

p13

p13

cso30:i:ME_Phosphorylation

cso30:i:CC_Cytosol

--

MO000017065 e25

e23

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c35 : 1
stoichiometry:c37 : 1
stoichiometry:c36 : 1

m1957*m25*0.1

nodelay

--

true

0

false

PMID: 18226603, 12626342 In a related topic, crocidolite asbestos has also been shown to trigger the PKC (delta isoform specific) pathway leading to apoptosis, but it was not linked with SR activation.

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162.0, 579.0
26.0, 26.0

p14

p14

cso30:i:CE_CellDeath

cso30:i:CC_Extracellular

--

e23

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c38 : 1

m23*0.1

nodelay

--

true

0

false

PMID: 18226603, 12626342 In a related topic, crocidolite asbestos has also been shown to trigger the PKC (delta isoform specific) pathway leading to apoptosis, but it was not linked with SR activation.

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519.0, 281.0
25.0, 25.0

p15

p15

cso30:i:ME_Phosphorylation

cso30:i:CC_Cytosol

--

MO000101490 e28

e26

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c39 : 1
stoichiometry:c41 : 1
stoichiometry:c40 : 1

m74475*m28*0.1

nodelay

--

true

0

false

PMID: 18226603, 10593991 Fong and Le identified serine phosphorylation after ac-LDL stimulation that could be disrupted using SR-A receptor mutants on CHO and COS cells at the Ser49 and Asp25 amino acid sites.

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327.0, 464.0
25.0, 25.0

p16

p16

cso30:i:ME_Binding

cso30:i:CC_Cytosol

--

MO000101490 MO000107436

e29

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c42 : 1
stoichiometry:c43 : 1
stoichiometry:c44 : 1

m74475*m341431*0.1

nodelay

--

true

0

false

PMID: 18226603, 11390374 In a study by Hsu et al., it was demonstrated that two different SR-A ligands (ox-LDL and fucoidan) could trigger differential cell responses using slightly different protein kinase signaling pathways.

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328.0, 513.0
24.0, 24.0

p17

p17

cso30:i:ME_Binding

cso30:i:CC_Cytosol

--

e31 MO000101490

e30

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c45 : 1
stoichiometry:c46 : 1
stoichiometry:c47 : 1

m31*m74475*0.1

nodelay

--

true

0

false

PMID: 18226603, 11390374 In a study by Hsu et al., it was demonstrated that two different SR-A ligands (ox-LDL and fucoidan) could trigger differential cell responses using slightly different protein kinase signaling pathways.

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459.0, 1224.0
25.0, 25.0

p18

p18

cso30:i:ME_GeneExpression

cso30:i:CC_Nucleoplasm

--

e33

G013287

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c49 : 1
stoichiometry:c48 : 1

m33*0.1

nodelay

--

true

0

false

PMID: 18226603, 15218052 For example, the presence of TLR-4 has been shown to be important for the induction of MARCO expression using TLR-4 mutant mice.

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823.0, 1139.0
26.0, 26.0

p19

p19

cso30:i:ME_GeneExpression

cso30:i:CC_Nucleoplasm

--

MO000016882 e13 e12

G010657

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c51 : 1
stoichiometry:c56 : 1
stoichiometry:c58 : 1
stoichiometry:c54 : 1

m155666*m13*0.1

nodelay

--

true

0

false

PMID: 18226603, 16339540 In addition, MARCO-null mice were associated with inhibited IL-12 production, whereas SR-A-null mice were associated with enhanced IL-12 production compared to wild-type mice in response to lipopolysaccharide (LPS) or IFN-gamma.

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643.0, 169.0
25.0, 25.0

p2

p2

cso30:i:ME_Binding

cso30:i:CC_Extracellular

--

e6 MO000101490

e12

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c4 : 1
stoichiometry:c5 : 1
stoichiometry:c6 : 1

m6*m74475*0.1

nodelay

--

true

0

false

PMID: 18226603, 11899233, 7541421 The SR most associated with AM silica binding are SR-AI, SR-AII, and MARCO.

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797.0, 1178.0
25.0, 25.0

p20

p20

cso30:i:ME_GeneExpression

cso30:i:CC_Nucleoplasm

--

MO000016665 e12

G010657

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c50 : 1
stoichiometry:c60 : 1
stoichiometry:c59 : 1

m1639*0.1

nodelay

--

true

0

false

PMID: 18226603, 16339540 In addition, MARCO-null mice were associated with inhibited IL-12 production, whereas SR-A-null mice were associated with enhanced IL-12 production compared to wild-type mice in response to lipopolysaccharide (LPS) or IFN-gamma.

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887.0, 1096.0
25.0, 25.0

p21

p21

cso30:i:ME_Translation

cso30:i:CC_Cytosol

--

G010657 e13 e12

MO000017265

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c53 : 1
stoichiometry:c55 : 1
stoichiometry:c57 : 1
stoichiometry:c52 : 1

m93589*m13*0.1

nodelay

--

true

0

false

PMID: 18226603, 16339540 In addition, MARCO-null mice were associated with inhibited IL-12 production, whereas SR-A-null mice were associated with enhanced IL-12 production compared to wild-type mice in response to lipopolysaccharide (LPS) or IFN-gamma.

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974.0, 311.0
27.0, 27.0

p22

p22

cso30:i:ME_UnknownProduction

cso30:i:CC_Cytosol

--

e6

MO000000306

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c61 : 1
stoichiometry:c62 : 1

m6*0.1

nodelay

--

true

0

false

PMID: 18226603, 11570673 Adhesion protein ICAM-1, although not directly involved in silica uptake, is upregulated on AM and other cell types with in vivo and in vitro silica exposure and believed to initiate the inflammatory PMN influx into the lungs.

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812.0, 341.0
23.0, 23.0

p23

p23

cso30:i:ME_UnknownProduction

cso30:i:CC_Cytosol

--

e12 e77

MO000008272

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c67 : 1
stoichiometry:c162 : 1
stoichiometry:c63 : 1

m12*0.1

nodelay

--

true

0

false

PMID: 18226603, 12788471 There are several possible sources of free radicals resulting from silica internalization, including particle-derived reactive oxygen species (ROS), cell-derived ROS and reactive nitrogen species (RNS), and the interaction of particle- and cell-derived free radicals producing peroxynitrite (ONOOO2radical) from nitric oxide (NOradical) and superoxide anion (O2radical) PMID: 18226603, 10516215 It was also noted in this study that the GSH precursor (N-acetylcysteine) decreased ROS formation, resulting in reduced membrane permeability changes and DNA damage.

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816.0, 385.0
23.0, 23.0

p24

p24

cso30:i:ME_UnknownProduction

cso30:i:CC_Cytosol

--

e12 e77

e32

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c68 : 1
stoichiometry:c161 : 1
stoichiometry:c64 : 1

m12*0.1

nodelay

--

true

0

false

PMID: 18226603, 12788471 There are several possible sources of free radicals resulting from silica internalization, including particle-derived reactive oxygen species (ROS), cell-derived ROS and reactive nitrogen species (RNS), and the interaction of particle- and cell-derived free radicals producing peroxynitrite (ONOOO2radical) from nitric oxide (NOradical) and superoxide anion (O2radical) PMID: 18226603, 10516215 It was also noted in this study that the GSH precursor (N-acetylcysteine) decreased ROS formation, resulting in reduced membrane permeability changes and DNA damage.

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816.0, 433.0
23.0, 23.0

p25

p25

cso30:i:ME_UnknownProduction

cso30:i:CC_Cytosol

--

e12

e34

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c69 : 1
stoichiometry:c65 : 1

m12*0.1

nodelay

--

true

0

false

PMID: 18226603, 12788471 There are several possible sources of free radicals resulting from silica internalization, including particle-derived reactive oxygen species (ROS), cell-derived ROS and reactive nitrogen species (RNS), and the interaction of particle- and cell-derived free radicals producing peroxynitrite (ONOOO2radical) from nitric oxide (NOradical) and superoxide anion (O2radical)

Go back
816.0, 481.0
23.0, 23.0

p26

p26

cso30:i:ME_UnknownProduction

cso30:i:CC_Cytosol

--

e12 e38 e39 MO000008272 e32

e35

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c70 : 1
stoichiometry:c75 : 1
stoichiometry:c76 : 1
stoichiometry:c79 : 1
stoichiometry:c80 : 1
stoichiometry:c66 : 1

m12*m38*m39*m1063*m32*0.1

nodelay

--

true

0

false

PMID: 18226603, 12788471 There are several possible sources of free radicals resulting from silica internalization, including particle-derived reactive oxygen species (ROS), cell-derived ROS and reactive nitrogen species (RNS), and the interaction of particle- and cell-derived free radicals producing peroxynitrite (ONOOO2radical) from nitric oxide (NOradical) and superoxide anion (O2radical)

Go back
816.0, 525.0
23.0, 23.0

p27

p27

cso30:i:ME_UnknownProduction

cso30:i:CC_Cytosol

--

e12

e39

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c71 : 1
stoichiometry:c73 : 1

m12*0.1

nodelay

--

true

0

false

PMID: 18226603, 7705309 In addition, the AM process of silica phagocytosis has been reported to produce O2radical, hydrogen peroxide (H2O2), and hydroxyl radicals (HOradical)

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820.0, 577.0
23.0, 23.0

p28

p28

cso30:i:ME_UnknownProduction

cso30:i:CC_Cytosol

--

e12

e37

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c72 : 1
stoichiometry:c74 : 1

m12*0.1

nodelay

--

true

0

false

PMID: 18226603, 7705309 In addition, the AM process of silica phagocytosis has been reported to produce O2radical, hydrogen peroxide (H2O2), and hydroxyl radicals (HOradical)

Go back
815.0, 624.0
26.0, 26.0

p29

p29

cso30:i:ME_UnknownProduction

cso30:i:CC_Cytosol

--

e12 e64

e36

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c77 : 1
stoichiometry:c127 : 1
stoichiometry:c78 : 1

m12*m69*0.1

nodelay

--

true

0

false

PMID: 18226603, 7705309 In addition, the AM process of silica phagocytosis has been reported to produce O2radical, hydrogen peroxide (H2O2), and hydroxyl radicals (HOradical) PMID: 18226603 The hydroxyl radical is the most potentially damaging ROS (due to very short half-life, high reactivity, and lack of effective elimination) to the lung, but it is produced to any significant degree only in the presence of contaminants such as iron (Fenton reaction).

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779.0, 157.0
25.0, 25.0

p3

p3

cso30:i:ME_Binding

cso30:i:CC_Extracellular

--

e6 e16

e13

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c8 : 1
stoichiometry:c11 : 1
stoichiometry:c7 : 1

m6*m16*0.1

nodelay

--

true

0

false

PMID: 18226603, 11899233, 7541421 The SR most associated with AM silica binding are SR-AI, SR-AII, and MARCO. PMID: 18226603, 17405873 Ojala et al. propose that multiple MARCO receptors can group together on the surface of the cell, allowing the SRCR regions to dimerize or oligomerize, creating a much larger binding surface area that is capable of binding physically large ligands such as silica and bacteria.

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773.0, 1030.0
30.0, 30.0

p30

p30

cso30:i:ME_DNADamage

cso30:i:CC_Cytosol

--

MO000008272 e77

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c82 : 1
stoichiometry:c164 : 1

m1063*0.1

nodelay

--

true

0

false

PMID: 18226603, 8603472, 8394268, 7705289 Evidence strongly suggests that silica-derived ROS are directly responsible for in vitro DNA damage [81], [82] and [83], various morphological changes including apoptosis in in vitro cell cultures [79], [84] and [85], and acute lung damage in vivo. PMID: 18226603, 10516215 It was also noted in this study that the GSH precursor (N-acetylcysteine) decreased ROS formation, resulting in reduced membrane permeability changes and DNA damage.

Go back
757.0, 990.0
30.0, 30.0

p31

p31

cso30:i:ME_DNADamage

cso30:i:CC_Nucleoplasm

--

e77 e32

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c163 : 1
stoichiometry:c81 : 1

m32*0.1

nodelay

--

true

0

false

PMID: 18226603, 8603472, 8394268, 7705289 Evidence strongly suggests that silica-derived ROS are directly responsible for in vitro DNA damage [81], [82] and [83], various morphological changes including apoptosis in in vitro cell cultures [79], [84] and [85], and acute lung damage in vivo. PMID: 18226603, 10516215 It was also noted in this study that the GSH precursor (N-acetylcysteine) decreased ROS formation, resulting in reduced membrane permeability changes and DNA damage.

Go back
1201.0, 322.0
27.0, 27.0

p32

p32

cso30:i:CE_CellDeath

cso30:i:CC_Extracellular

--

MO000008272

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c83 : 1

m1063*0.1

nodelay

--

true

0

false

PMID: 18226603, 11570678, 10963957, 15242185 Evidence strongly suggests that silica-derived ROS are directly responsible for in vitro DNA damage [81], [82] and [83], various morphological changes including apoptosis in in vitro cell cultures [79], [84] and [85], and acute lung damage in vivo.

Go back
1182.0, 406.0
27.0, 27.0

p33

p33

cso30:i:CE_CellDeath

cso30:i:CC_Extracellular

--

e32

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c84 : 1

m32*0.1

nodelay

--

true

0

false

PMID: 18226603, 11570678, 10963957, 15242185 Evidence strongly suggests that silica-derived ROS are directly responsible for in vitro DNA damage [81], [82] and [83], various morphological changes including apoptosis in in vitro cell cultures [79], [84] and [85], and acute lung damage in vivo.

Go back
519.0, 996.0
25.0, 25.0

p34

p34

cso30:i:ME_UnknownActivation

cso30:i:CC_Cytosol

--

e23 MO000000058

e40

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c91 : 1
stoichiometry:c92 : 1
stoichiometry:c103 : 1

m23*m40*0.1

nodelay

--

true

0

false

PMID: 18226603 For example, SR may be the way silica binds to the AM initially, followed by particle endocytosis complete with a respiratory burst creating ROS and RNS, followed by PKC-mediated MAP kinase signaling cascades resulting in AP-1 and NF-kappaB activation, which ultimately results in cytokine release (IL-1beta, MIP-1, MCP-1, and TNF-alpha).

Go back
479.0, 596.0
25.0, 25.0

p35

p35

cso30:i:ME_Phosphorylation

cso30:i:CC_Cytosol

--

MO000000018 e23

MO000038305

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c87 : 1
stoichiometry:c85 : 1
stoichiometry:c88 : 1

m41*m23*0.1

nodelay

--

true

0

false

PMID: 18226603, 10471390 For example, silica-induced free radicals activated MEK and ERK phosphorylation in a rat fibroblast cell line. PMID: 18226603 For example, SR may be the way silica binds to the AM initially, followed by particle endocytosis complete with a respiratory burst creating ROS and RNS, followed by PKC-mediated MAP kinase signaling cascades resulting in AP-1 and NF-kappaB activation, which ultimately results in cytokine release (IL-1beta, MIP-1, MCP-1, and TNF-alpha).

Go back
458.0, 639.0
27.0, 27.0

p36

p36

cso30:i:ME_Phosphorylation

cso30:i:CC_Cytosol

--

MO000000011 e23

MO000038306

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c89 : 1
stoichiometry:c86 : 1
stoichiometry:c90 : 1

m42*m23*0.1

nodelay

--

true

0

false

PMID: 18226603, 10471390 For example, silica-induced free radicals activated MEK and ERK phosphorylation in a rat fibroblast cell line. PMID: 18226603 For example, SR may be the way silica binds to the AM initially, followed by particle endocytosis complete with a respiratory burst creating ROS and RNS, followed by PKC-mediated MAP kinase signaling cascades resulting in AP-1 and NF-kappaB activation, which ultimately results in cytokine release (IL-1beta, MIP-1, MCP-1, and TNF-alpha).

Go back
510.0, 827.0
27.0, 27.0

p37

p37

cso30:i:ME_UnknownActivation

cso30:i:CC_Cytosol

--

MO000000022 MO000038306

e41

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c93 : 1
stoichiometry:c95 : 1
stoichiometry:c94 : 1

m43*m16522*0.1

nodelay

--

true

0

false

PMID: 18226603, 10521445 Luciferase reporter mice have also been used to show AP-1 activation in vivo after silica inhalation through ERK and p38 MAPK signaling pathways.

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579.0, 984.0
25.0, 25.0

p38

p38

cso30:i:ME_UnknownActivation

cso30:i:CC_Nucleoplasm

--

e41 e27 e42

MO000000276

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c96 : 1
stoichiometry:c97 : 1
stoichiometry:c102 : 1
stoichiometry:c98 : 1

m44*m27*m46*0.1

nodelay

--

true

0

false

PMID: 18226603, 10521445 Luciferase reporter mice have also been used to show AP-1 activation in vivo after silica inhalation through ERK and p38 MAPK signaling pathways. PMID: 18226603, 11280724 In vitro evidence for silica-initiated oxidative stress-induced AP-1 activation associated with JNK signaling, via c-Jun-NH2-terminal amino kinases, can be found in Shukla et al. PMID: 18226603 For example, SR may be the way silica binds to the AM initially, followed by particle endocytosis complete with a respiratory burst creating ROS and RNS, followed by PKC-mediated MAP kinase signaling cascades resulting in AP-1 and NF-kappaB activation, which ultimately results in cytokine release (IL-1beta, MIP-1, MCP-1, and TNF-alpha).

Go back
521.0, 702.0
29.0, 29.0

p39

p39

cso30:i:ME_UnknownActivation

cso30:i:CC_Cytosol

--

MO000038305 MO000000023

e42

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c99 : 1
stoichiometry:c100 : 1
stoichiometry:c101 : 1

m16521*m45*0.1

nodelay

--

true

0

false

PMID: 18226603, 11280724 In vitro evidence for silica-initiated oxidative stress-induced AP-1 activation associated with JNK signaling, via c-Jun-NH2-terminal amino kinases, can be found in Shukla et al.

Go back
826.0, 296.0
27.0, 27.0

p4

p4

cso30:i:ME_Dimerization

cso30:i:CC_Cytosol

--

MO000042355

e16

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c9 : 1
stoichiometry:c10 : 1

m20155*0.1

nodelay

--

true

0

false

PMID: 18226603, 17405873 Ojala et al. propose that multiple MARCO receptors can group together on the surface of the cell, allowing the SRCR regions to dimerize or oligomerize, creating a much larger binding surface area that is capable of binding physically large ligands such as silica and bacteria.

Go back
386.0, 831.0
27.0, 27.0

p40

p40

cso30:i:ME_UnknownActivation

cso30:i:CC_Cytosol

--

e43 e12

e44

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c104 : 1
stoichiometry:c106 : 1
stoichiometry:c105 : 1

m48*m12*0.1

nodelay

--

true

0

false

PMID: 18226603, 17158358 In a rat AM model, Liu et al. demonstrated that TNF-alpha and IL-1beta release after silica exposure was mediated through phosphatidylcholine-specific phospholipase C regulated in a redox-dependent fashion.

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351.0, 1128.0
25.0, 25.0

p41

p41

cso30:i:ME_Translation

cso30:i:CC_Cytosol

--

G010329 e44 e40

MO000000289

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c109 : 1
stoichiometry:c111 : 1
stoichiometry:c113 : 1
stoichiometry:c107 : 1

m93309*m49*m47*0.1

nodelay

--

true

0

false

PMID: 18226603, 17158358 In a rat AM model, Liu et al. demonstrated that TNF-alpha and IL-1beta release after silica exposure was mediated through phosphatidylcholine-specific phospholipase C regulated in a redox-dependent fashion. PMID: 18226603 For example, SR may be the way silica binds to the AM initially, followed by particle endocytosis complete with a respiratory burst creating ROS and RNS, followed by PKC-mediated MAP kinase signaling cascades resulting in AP-1 and NF-kappaB activation, which ultimately results in cytokine release (IL-1beta, MIP-1, MCP-1, and TNF-alpha).

Go back
331.0, 1172.0
25.0, 25.0

p42

p42

cso30:i:ME_Translation

cso30:i:CC_Cytosol

--

G010389 e44 e40

MO000016597

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c110 : 1
stoichiometry:c112 : 1
stoichiometry:c114 : 1
stoichiometry:c108 : 1

m93364*m49*m47*0.1

nodelay

--

true

0

false

PMID: 18226603, 17158358 In a rat AM model, Liu et al. demonstrated that TNF-alpha and IL-1beta release after silica exposure was mediated through phosphatidylcholine-specific phospholipase C regulated in a redox-dependent fashion. PMID: 18226603 For example, SR may be the way silica binds to the AM initially, followed by particle endocytosis complete with a respiratory burst creating ROS and RNS, followed by PKC-mediated MAP kinase signaling cascades resulting in AP-1 and NF-kappaB activation, which ultimately results in cytokine release (IL-1beta, MIP-1, MCP-1, and TNF-alpha).

Go back
971.0, 1220.0
25.0, 25.0

p43

p43

cso30:i:ME_Translation

cso30:i:CC_Cytosol

--

e45 e12

e46

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c116 : 1
stoichiometry:c123 : 1
stoichiometry:c115 : 1

m63*m12*0.1

nodelay

--

true

0

false

PMID: 18226603, 10438654, 9747602 The inflammatory cytokines most commonly associated with silica-induced free radicals are TNF-alpha, IL-1beta, MIP-1, MIP-2, MCP-1 [103], and IL-8 (after TNF-alpha priming) [104].

Go back
970.0, 1259.0
27.0, 27.0

p44

p44

cso30:i:ME_Translation

cso30:i:CC_Extracellular

--

e47 e12

e48

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c117 : 1
stoichiometry:c124 : 1
stoichiometry:c118 : 1

m65*m12*0.1

nodelay

--

true

0

false

PMID: 18226603, 10438654, 9747602 The inflammatory cytokines most commonly associated with silica-induced free radicals are TNF-alpha, IL-1beta, MIP-1, MIP-2, MCP-1 [103], and IL-8 (after TNF-alpha priming) [104].

Go back
971.0, 1304.0
25.0, 25.0

p45

p45

cso30:i:ME_Translation

cso30:i:CC_Cytosol

--

G010815 e12

MO000017280

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c120 : 1
stoichiometry:c125 : 1
stoichiometry:c119 : 1

m93710*m12*0.1

nodelay

--

true

0

false

PMID: 18226603, 10438654, 9747602 The inflammatory cytokines most commonly associated with silica-induced free radicals are TNF-alpha, IL-1beta, MIP-1, MIP-2, MCP-1 [103], and IL-8 (after TNF-alpha priming) [104].

Go back
970.0, 1347.0
27.0, 27.0

p46

p46

cso30:i:ME_Translation

cso30:i:CC_Cytosol

--

e49 e12

MO000017264

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c122 : 1
stoichiometry:c126 : 1
stoichiometry:c121 : 1

m67*m12*0.1

nodelay

--

true

0

false

PMID: 18226603, 10438654, 9747602 The inflammatory cytokines most commonly associated with silica-induced free radicals are TNF-alpha, IL-1beta, MIP-1, MIP-2, MCP-1 [103], and IL-8 (after TNF-alpha priming) [104].

Go back
528.0, 345.0
24.0, 24.0

p47

p47

cso30:i:ME_UnknownProduction

cso30:i:CC_Cytosol

--

e12 e63

MO000042963

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c130 : 1
stoichiometry:c132 : 1
stoichiometry:c128 : 1

1.0*0.1

nodelay

--

true

0

false

PMID: 18226603, 8277518 The untreated silica caused a significant reduction in lysosomal enzyme (cathepsin B) activity that was inhibited by silica pretreatment with dipalmitoyl lecithin or the presence of ammonium chloride.

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527.0, 388.0
25.0, 25.0

p48

p48

cso30:i:ME_UnknownProduction

cso30:i:CC_Cytosol

--

e12 e65

MO000042963

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c131 : 1
stoichiometry:c133 : 1
stoichiometry:c129 : 1

1.0*0.1

nodelay

--

true

0

false

PMID: 18226603, 8277518 The untreated silica caused a significant reduction in lysosomal enzyme (cathepsin B) activity that was inhibited by silica pretreatment with dipalmitoyl lecithin or the presence of ammonium chloride.

Go back
816.0, 669.0
23.0, 23.0

p49

p49

cso30:i:ME_UnknownProduction

cso30:i:CC_Cytosol

--

e12

e66

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c140 : 1
stoichiometry:c134 : 1

m12*0.1

nodelay

--

true

0

false

PMID: 18226603, 12781626, 11275417 Several other studies found silica-induced increases in PL and SP [17] and [18], including specific increases in SP-A [19] and [20], SP-D [19] and [21], vitamin E [22], and phosphatidyl inositol [23].

Go back
390.0, 160.0
27.0, 27.0

p5

p5

cso30:i:ME_Binding

cso30:i:CC_Extracellular

--

e17 e5

e18

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c12 : 1
stoichiometry:c15 : 1
stoichiometry:c19 : 1

m17*m5*0.1

nodelay

--

true

0

false

PMID: 18226603, 7541421 Another unresolved issue with the receptor-mediated hypothesis is that nontoxic particles such as titanium dioxide are known to bind to the same receptors without triggering the death response.

Go back
811.0, 704.0
25.0, 25.0

p50

p50

cso30:i:ME_UnknownProduction

cso30:i:CC_Cytosol

--

e12

e67

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c141 : 1
stoichiometry:c135 : 1

m12*0.1

nodelay

--

true

0

false

PMID: 18226603, 12781626, 11275417 Several other studies found silica-induced increases in PL and SP [17] and [18], including specific increases in SP-A [19] and [20], SP-D [19] and [21], vitamin E [22], and phosphatidyl inositol [23].

Go back
809.0, 744.0
26.0, 26.0

p51

p51

cso30:i:ME_UnknownProduction

cso30:i:CC_Cytosol

--

e12

e68

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c142 : 1
stoichiometry:c136 : 1

m12*0.1

nodelay

--

true

0

false

PMID: 18226603, 10969075, 10749748, 12611476 Several other studies found silica-induced increases in PL and SP [17] and [18], including specific increases in SP-A [19] and [20], SP-D [19] and [21], vitamin E [22], and phosphatidyl inositol [23].

Go back
800.0, 789.0
23.0, 23.0

p52

p52

cso30:i:ME_UnknownProduction

cso30:i:CC_Cytosol

--

e12

e69

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c143 : 1
stoichiometry:c137 : 1

m12*0.1

nodelay

--

true

0

false

PMID: 18226603, 10969075, 10749748, 12611476 Several other studies found silica-induced increases in PL and SP [17] and [18], including specific increases in SP-A [19] and [20], SP-D [19] and [21], vitamin E [22], and phosphatidyl inositol [23].

Go back
787.0, 828.0
25.0, 25.0

p53

p53

cso30:i:ME_UnknownProduction

cso30:i:CC_Cytosol

--

e12

e70

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c144 : 1
stoichiometry:c138 : 1

m12*0.1

nodelay

--

true

0

false

PMID: 18226603, 8968411, 11218049 Several other studies found silica-induced increases in PL and SP [17] and [18], including specific increases in SP-A [19] and [20], SP-D [19] and [21], vitamin E [22], and phosphatidyl inositol [23].

Go back
775.0, 868.0
25.0, 25.0

p54

p54

cso30:i:ME_UnknownProduction

cso30:i:CC_Cytosol

--

e12

MO000016797

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c145 : 1
stoichiometry:c139 : 1

m12*0.1

nodelay

--

true

0

false

PMID: 18226603, 8968411, 11218049 Several other studies found silica-induced increases in PL and SP [17] and [18], including specific increases in SP-A [19] and [20], SP-D [19] and [21], vitamin E [22], and phosphatidyl inositol [23].

Go back
761.0, 906.0
22.0, 22.0

p55

p55

cso30:i:ME_UnknownProduction

cso30:i:CC_Cytosol

--

e12

e71

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c147 : 1
stoichiometry:c146 : 1

m12*0.1

nodelay

--

true

0

false

PMID: 18226603, 11218049 In contrast, Seiler et al. found a dose-dependent decrease in phosphatidyl glycerol in response to silica.

Go back
332.0, 297.0
23.0, 23.0

p56

p56

cso30:i:ME_Binding

cso30:i:CC_Cytosol

--

MO000101490 e72

e73

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c148 : 1
stoichiometry:c149 : 1
stoichiometry:c150 : 1

m74475*m77*0.1

nodelay

--

true

0

false

PMID: 18226603, 11437644 Further evidence from the same group determined that the SR-A blocking antibody (2F-8) could significantly attenuate caspase activity after silica exposure in murine MH-S cells.

Go back
319.0, 372.0
25.0, 25.0

p57

p57

cso30:i:ME_UnknownActivation

cso30:i:CC_Cytosol

--

MO000016907 e73

e74

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c151 : 1
stoichiometry:c153 : 1
stoichiometry:c152 : 1

m1822*0.1

nodelay

--

true

0

false

PMID: 18226603, 11437644 Further evidence from the same group determined that the SR-A blocking antibody (2F-8) could significantly attenuate caspase activity after silica exposure in murine MH-S cells.

Go back
1204.0, 273.0
23.0, 23.0

p58

p58

cso30:i:CE_CellDeath

cso30:i:CC_Extracellular

--

e13

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c154 : 1

m13*0.1

nodelay

--

true

0

false

PMID: 18226603, 16984918 Studies using MARCO¡Ý/¡Ý, SR-AI/II¡Ý/¡Ý, and CD36¡Ý/¡Ý single and double null combinations on the C57BL/6 mouse model demonstrated that MARCO was exclusively associated with in vitro silica-induced AM apoptosis and cytotoxicity, in addition to silica binding and uptake.

Go back
691.0, 784.0
25.0, 25.0

p59

p59

cso30:i:ME_UnknownProduction

cso30:i:CC_Cytosol

--

e12

MO000021289

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c156 : 1
stoichiometry:c160 : 1

m12*0.1

nodelay

--

true

0

false

PMID: 18226603, 1323223, 1316905 Further evidence for silica-induced ROS in rat model lungs comes from observed increases in antioxidant enzymes such as manganese superoxide dismutase (MnSOD) from type II epithelial cells [90], along with increased SOD and glutathione peroxidase mRNA in rat lungs after silica inhalation.

Go back
587.0, 161.0
25.0, 25.0

p6

p6

cso30:i:ME_Binding

cso30:i:CC_Extracellular

--

e17 MO000101490

e19

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c13 : 1
stoichiometry:c17 : 1
stoichiometry:c16 : 1

m17*m74475*0.1

nodelay

--

true

0

false

PMID: 18226603, 7541421 Another unresolved issue with the receptor-mediated hypothesis is that nontoxic particles such as titanium dioxide are known to bind to the same receptors without triggering the death response.

Go back
722.0, 987.0
20.0, 20.0

p60

p60

cso30:i:ME_UnknownProduction

cso30:i:CC_Cytosol

--

e12

e76

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c157 : 1
stoichiometry:c158 : 1

m12*0.1

nodelay

--

true

0

false

PMID: 18226603, 1323223, 1316905 Further evidence for silica-induced ROS in rat model lungs comes from observed increases in antioxidant enzymes such as manganese superoxide dismutase (MnSOD) from type II epithelial cells [90], along with increased SOD and glutathione peroxidase mRNA in rat lungs after silica inhalation.

Go back
679.0, 740.0
25.0, 25.0

p61

p61

cso30:i:ME_UnknownProduction

cso30:i:CC_Cytosol

--

e12

e75

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c155 : 1
stoichiometry:c159 : 1

m12*0.1

nodelay

--

true

0

false

PMID: 18226603, 1323223, 1316905 Further evidence for silica-induced ROS in rat model lungs comes from observed increases in antioxidant enzymes such as manganese superoxide dismutase (MnSOD) from type II epithelial cells [90], along with increased SOD and glutathione peroxidase mRNA in rat lungs after silica inhalation.

Go back
668.0, 709.0
23.0, 23.0

p62

p62

cso30:i:ME_UnknownProduction

cso30:i:CC_Cytosol

--

e12

MO000007321

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c166 : 1
stoichiometry:c165 : 1

m12*0.1

nodelay

--

true

0

false

PMID: 18226603, 15893544 Both ex vivo exposures of AM and in vitro exposures of bone-marrow-derived macrophages to silica in the murine model have shown increased (relative to basal production) lymphocyte cytokines (IL-13 and IFN-gamma) using an antigen-presenting cell (APC) assay in macrophage/lymphocyte cocultures.

Go back
653.0, 670.0
21.0, 21.0

p63

p63

cso30:i:ME_UnknownProduction

cso30:i:CC_Cytosol

--

e12

e79

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c167 : 1
stoichiometry:c168 : 1

m12*0.1

nodelay

--

true

0

false

PMID: 18226603, 15893544 Both ex vivo exposures of AM and in vitro exposures of bone-marrow-derived macrophages to silica in the murine model have shown increased (relative to basal production) lymphocyte cytokines (IL-13 and IFN-gamma) using an antigen-presenting cell (APC) assay in macrophage/lymphocyte cocultures. PMID: 18226603, 11570676 This result was supported by another study using human AM exposed in vitro to silica, resulting in increased lymphocyte cytokines (IL-4 and IFN-gamma), using a human APC cell culture model.

Go back
703.0, 836.0
25.0, 25.0

p64

p64

cso30:i:ME_UnknownProduction

cso30:i:CC_Cytosol

--

e12

MO000017053

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c170 : 1
stoichiometry:c169 : 1

m12*0.1

nodelay

--

true

0

false

PMID: 18226603, 11570676 This result was supported by another study using human AM exposed in vitro to silica, resulting in increased lymphocyte cytokines (IL-4 and IFN-gamma), using a human APC cell culture model.

Go back
252.0, 1273.0
23.0, 23.0

p65

p65

cso30:i:ME_Translocation

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

e80 e12

MO000081880

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c171 : 1
stoichiometry:c173 : 1
stoichiometry:c172 : 1

m85*m12*0.1

nodelay

--

true

0

false

PMID: 18226603, 12857937 This study concluded that the apoptotic signaling pathway involved lysosomal leakage resulting in cathepsin D release, and acidic sphingomyelinase activation, which preceded the mitochondrial depolarization and caspase 3 and 9 activation (reported earlier by the same group) caused by silica exposure.

Go back
180.0, 1349.0
23.0, 23.0

p66

p66

cso30:i:ME_UnknownActivation

cso30:i:CC_Cytosol

--

MO000017824 e12

e81

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c174 : 1
stoichiometry:c180 : 1
stoichiometry:c175 : 1

m2576*m12*0.1

nodelay

--

true

0

false

PMID: 18226603, 12857937 This study concluded that the apoptotic signaling pathway involved lysosomal leakage resulting in cathepsin D release, and acidic sphingomyelinase activation, which preceded the mitochondrial depolarization and caspase 3 and 9 activation (reported earlier by the same group) caused by silica exposure.

Go back
395.0, 1455.0
25.0, 25.0

p67

p67

cso30:i:ME_UnknownActivation

cso30:i:CC_Cytosol

--

MO000016924 e12

e78

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c176 : 1
stoichiometry:c181 : 1
stoichiometry:c177 : 1

m1839*m12*0.1

nodelay

--

true

0

false

PMID: 18226603, 12857937 This study concluded that the apoptotic signaling pathway involved lysosomal leakage resulting in cathepsin D release, and acidic sphingomyelinase activation, which preceded the mitochondrial depolarization and caspase 3 and 9 activation (reported earlier by the same group) caused by silica exposure.

Go back
510.0, 1474.0
27.0, 27.0

p68

p68

cso30:i:ME_UnknownActivation

cso30:i:CC_Extracellular

--

MO000016987 e12

e82

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c178 : 1
stoichiometry:c182 : 1
stoichiometry:c179 : 1

m1891*m12*0.1

nodelay

--

true

0

false

PMID: 18226603, 12857937 This study concluded that the apoptotic signaling pathway involved lysosomal leakage resulting in cathepsin D release, and acidic sphingomyelinase activation, which preceded the mitochondrial depolarization and caspase 3 and 9 activation (reported earlier by the same group) caused by silica exposure.

Go back
507.0, 1531.0
25.0, 25.0

p69

p69

cso30:i:CE_CellDeath

cso30:i:CC_Extracellular

--

e78 e82

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c183 : 1
stoichiometry:c184 : 1

m83*m87*0.1

nodelay

--

true

0

false

PMID: 18226603 This then leads to mitochondrial depolarization, caspase 3 and caspase 9 activation, and apoptosis.

Go back
979.0, 153.0
25.0, 25.0

p7

p7

cso30:i:ME_Binding

cso30:i:CC_Extracellular

--

e17 MO000042355

e20

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c14 : 1
stoichiometry:c18 : 1
stoichiometry:c20 : 1

m17*m20155*0.1

nodelay

--

true

0

false

PMID: 18226603, 7541421 Another unresolved issue with the receptor-mediated hypothesis is that nontoxic particles such as titanium dioxide are known to bind to the same receptors without triggering the death response.

Go back
163.0, 676.0
25.0, 25.0

p8

p8

cso30:i:ME_Binding

cso30:i:CC_Extracellular

--

MO000021135 e22

e14

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c21 : 1
stoichiometry:c26 : 1
stoichiometry:c27 : 1

m5516*m22*0.1

nodelay

--

true

0

false

PMID: 18226603, 11785981 One study, using a synthetic bovine SR-A construct, demonstrated that heat-shock proteins HSP90 and HSP70, in addition to glyceraldehyde-3-phosphate dehydrogenase, bound to the cytoplasmic N-terminus of the SR.

Go back
162.0, 719.0
27.0, 27.0

p9

p9

cso30:i:ME_Binding

cso30:i:CC_Extracellular

--

MO000021614 e22

e15

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c22 : 1
stoichiometry:c24 : 1
stoichiometry:c25 : 1

m5956*m22*0.1

nodelay

--

true

0

false

PMID: 18226603, 11785981 One study, using a synthetic bovine SR-A construct, demonstrated that heat-shock proteins HSP90 and HSP70, in addition to glyceraldehyde-3-phosphate dehydrogenase, bound to the cytoplasmic N-terminus of the SR.

Go back
531.7345004769862, 126.0669940030169

c1

c1

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
852.0, 273.1631545689975

c10

c10

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
406.0, 717.0

c100

c100

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
541.0, 731.0

c101

c101

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
577.0, 835.0

c102

c102

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
532.0, 1021.0

c103

c103

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
368.0, 845.0

c104

c104

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
365.2680368629481, 858.0

c105

c105

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
420.3470745824917, 264.0

c106

c106

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
207.0, 1141.0

c107

c107

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
206.0, 1185.0

c108

c108

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
384.0, 1141.0

c109

c109

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
810.0608695236934, 185.2216722050282

c11

c11

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
364.0, 1185.0

c110

c110

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
352.0, 910.0

c111

c111

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
344.2441610143324, 910.0

c112

c112

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
383.9073257362567, 1079.0

c113

c113

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
363.91162311750423, 1079.0

c114

c114

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
996.0, 1233.0

c115

c115

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
806.0, 1233.0

c116

c116

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
786.0, 1273.0

c117

c117

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
997.0, 1273.0

c118

c118

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
996.0, 1317.0

c119

c119

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
403.69409355296824, 102.0921448600701

c12

c12

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
720.0, 1288.0

c120

c120

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
997.0, 1361.0

c121

c121

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
674.0, 1311.0

c122

c122

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
734.0, 57.06212323437086

c123

c123

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
733.0, 48.61601018451199

c124

c124

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
732.0, 32.55328847669858

c125

c125

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
720.3087043078416, 20.598585839938323

c126

c126

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
848.6967488338382, 597.0

c127

c127

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
500.0, 357.0

c128

c128

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
498.50986776965385, 370.64990554975276

c129

c129

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
542.0, 115.0

c13

c13

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
555.9999506447874, 264.0

c130

c130

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
555.9999845350493, 264.0

c131

c131

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
555.6280358709937, 338.0

c132

c132

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
537.0, 416.9861830329795

c133

c133

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
839.0, 681.0

c134

c134

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
836.0, 717.0

c135

c135

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
835.0, 757.0

c136

c136

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
823.0, 801.0

c137

c137

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
812.0, 841.0

c138

c138

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
800.0, 881.0

c139

c139

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
551.0, 104.0

c14

c14

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
736.0, 264.0

c140

c140

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
736.0, 264.0

c141

c141

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
735.0, 264.0

c142

c142

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
735.0, 264.0

c143

c143

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
734.0, 264.0

c144

c144

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
734.0, 264.0

c145

c145

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
783.0, 917.0

c146

c146

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
733.0, 264.0

c147

c147

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
362.999991794516, 266.0

c148

c148

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
140.0, 309.0

c149

c149

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
423.9502181615413, 184.96162435207853

c15

c15

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
284.2829318197008, 314.0

c150

c150

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
350.8415826524321, 358.0

c151

c151

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
344.0, 385.0

c152

c152

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
277.0, 352.0

c153

c153

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
961.0, 265.0

c154

c154

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
693.6366300188464, 264.0

c155

c155

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
705.3995009355511, 264.0

c156

c156

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
732.0, 264.0

c157

c157

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
732.0, 1007.0

c158

c158

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
660.0, 753.0

c159

c159

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
600.0, 186.0

c16

c16

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
679.0, 797.0

c160

c160

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
842.9023564925815, 399.878415508064

c161

c161

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
838.9883340756547, 354.3052725028083

c162

c162

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
790.992161361716, 695.0

c163

c163

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
806.9983014464108, 695.0

c164

c164

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
637.0, 721.0

c165

c165

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
681.8756066221666, 264.0

c166

c166

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
667.2266986386528, 264.0

c167

c167

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
635.0, 681.0

c168

c168

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
679.9958409147176, 849.0

c169

c169

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
613.7133772595955, 192.46406024173103

c17

c17

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
716.2236887300145, 264.0

c170

c170

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
283.0, 1285.0

c171

c171

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
204.75277739138355, 1269.9734342450795

c172

c172

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
71.55358283913063, 77.20926878661714

c173

c173

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
210.7090706633033, 1325.0

c174

c174

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
203.0, 1361.0

c175

c175

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
408.0, 1301.0

c176

c176

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
412.0, 1368.6890972431104

c177

c177

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
524.0, 1364.0

c178

c178

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
534.0, 1398.6064078549882

c179

c179

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
822.0, 166.02130735902261

c18

c18

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
56.2049236101484, 60.899362994337935

c180

c180

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
43.58923438933516, 43.613370087738474

c181

c181

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
28.143505072753328, 31.55936811971469

c182

c182

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
450.0, 1361.0

c183

c183

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
529.4736422780975, 1392.0

c184

c184

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
404.0, 187.0

c19

c19

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
532.0, 188.0

c2

c2

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
992.0, 178.0

c20

c20

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
134.0, 689.0

c21

c21

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
130.0, 733.0

c22

c22

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
132.0, 788.0

c23

c23

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
196.13188148017372, 696.0

c24

c24

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
189.0, 733.0

c25

c25

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
196.0, 689.0

c26

c26

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
188.0, 659.2829174186304

c27

c27

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
195.22018508287903, 703.0

c28

c28

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
191.0, 788.0

c29

c29

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
503.9691115068547, 188.0

c3

c3

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
518.998887248729, 264.0

c30

c30

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
444.0, 551.0

c31

c31

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
450.3174928327581, 566.0

c32

c32

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
428.0, 608.0

c33

c33

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
455.0, 1097.0

c34

c34

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
355.8878470836647, 551.0

c35

c35

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
348.0, 568.0

c36

c36

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
196.0, 564.0

c37

c37

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
196.0, 592.0

c38

c38

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
551.5410178012896, 256.0

c39

c39

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
656.0, 140.0

c4

c4

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
379.8384324702433, 262.59968009596804

c40

c40

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
201.0, 293.0

c41

c41

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
359.99999810283947, 266.0

c42

c42

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
146.0, 439.0

c43

c43

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
287.9981898404565, 477.0

c44

c44

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
151.0, 497.0

c45

c45

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
359.99999889793014, 266.0

c46

c46

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
287.9982644538249, 525.0

c47

c47

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
484.0, 1237.0

c48

c48

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
284.0, 1237.0

c49

c49

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
656.0, 202.0

c5

c5

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
829.9998880234031, 1191.0423274498594

c50

c50

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
856.9997094683067, 1149.0

c51

c51

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
912.0, 1111.0

c52

c52

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
768.0, 1118.4559341368413

c53

c53

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
775.5615216437443, 1156.0

c54

c54

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
918.7675321765424, 270.0

c55

c55

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
856.7166184079919, 270.0

c56

c56

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
740.0, 144.52758938259126

c57

c57

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
737.0, 116.50725586175531

c58

c58

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
775.8340833560568, 1184.6208448322877

c59

c59

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
668.0, 192.0

c6

c6

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
735.0, 72.50675489006028

c60

c60

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
657.0, 92.73517257833952

c61

c61

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
988.0, 338.0

c62

c62

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
835.0, 353.0

c63

c63

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
839.0, 397.0

c64

c64

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
839.0, 445.0

c65

c65

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
839.0, 493.0

c66

c66

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
747.0, 263.0

c67

c67

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
744.0, 264.0

c68

c68

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
741.0, 264.0

c69

c69

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
804.0, 176.0

c7

c7

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
739.0, 264.0

c70

c70

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
738.0, 264.0

c71

c71

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
737.0, 264.0

c72

c72

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
839.0, 537.0

c73

c73

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
843.0, 589.0

c74

c74

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
846.7575335791338, 458.0

c75

c75

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
845.9269205859564, 503.00222078299703

c76

c76

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
736.0, 264.0

c77

c77

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
841.0, 637.0

c78

c78

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
837.6530903510587, 368.0

c79

c79

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
679.0, 127.0

c8

c8

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
841.8148019150927, 412.0

c80

c80

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
794.9999994461958, 400.0

c81

c81

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
810.9999999993163, 354.0

c82

c82

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
915.0, 337.4190045278776

c83

c83

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
915.0, 398.0

c84

c84

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
443.0, 596.0

c85

c85

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
439.0, 608.0

c86

c86

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
512.0, 609.0

c87

c87

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
502.0, 621.0

c88

c88

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
399.0, 653.0

c89

c89

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
822.0, 271.0

c9

c9

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
477.0, 666.0

c90

c90

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
431.0, 608.0

c91

c91

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
498.0, 1019.4394686431388

c92

c92

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
491.0, 841.0

c93

c93

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
527.0, 854.0

c94

c94

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
518.0, 786.0

c95

c95

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
547.0, 921.0

c96

c96

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
601.8167349032339, 1016.0308274533255

c97

c97

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
592.0, 1009.0

c98

c98

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
536.0, 676.0

c99

c99

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back