KEGG   PATHWAY: csab04613
Entry
csab04613                   Pathway                                
Name
Neutrophil extracellular trap formation - Chlorocebus sabaeus (green monkey)
Description
Neutrophils play a central role in innate immune defense. One of the mechanisms of neutrophil action is the formation of neutrophil extracellular traps (NETs), the extracellular structures composed of chromatin coated with histones, proteases and granular and cytosolic proteins that help catch and kill microorganisms. NETs are formed by a process known as "NETosis" that can be triggered by microorganisms and endogenous stimuli, such as damage-associated molecular patterns and immune complexes, and involves activation in most cases of nicotinamide adenine dinucleotide phosphate (NADPH)-oxidase, which produces reactive oxygen species (ROS). Recent study has reported that there are two different mechanisms of NETosis, including a lytic NETosis and a vital NETosis. Lytic NETosis begins with nuclear delobulation and the disassembly of the nuclear envelope and continues with loss of cellular polarization, chromatin decondensation and plasma membrane rupture. Vital NETosis can occur independently of cell death and involves the secreted expulsion of nuclear chromatin that is accompanied by the release of granule proteins through degranulation.
Class
Organismal Systems; Immune system
Pathway map
csab04613  Neutrophil extracellular trap formation
csab04613

Organism
Chlorocebus sabaeus (green monkey) [GN:csab]
Gene
103215020  [KO:K05692]
103215048  [KO:K11253]
103215240  [KO:K11253]
103215243  [KO:K11253]
103215691  VDAC3; voltage dependent anion channel 3 [KO:K15041]
103215933  PPIF; peptidylprolyl isomerase F [KO:K09565] [EC:5.2.1.8]
103215964  VDAC2; voltage dependent anion channel 2 [KO:K15040]
103216062  H2AFY2; H2A histone family member Y2 [KO:K11251]
103216306  [KO:K11253]
103217237  [KO:K05692]
103217315  HAT1; histone acetyltransferase 1 [KO:K11303] [EC:2.3.1.48]
103218195  HDAC4; histone deacetylase 4 [KO:K11406] [EC:3.5.1.98]
103218442  VWF; von Willebrand factor [KO:K03900]
103218570  CLEC7A; C-type lectin domain family 7 member A [KO:K10074]
103218674  HIST4H4; histone cluster 4, H4 [KO:K11254]
103218675  H2AFJ; H2A histone family member J [KO:K11251]
103218914  C5; complement C5 [KO:K03994]
103218937  TLR4; toll like receptor 4 [KO:K10160]
103219323  [KO:K05692]
103219736  SYK; spleen associated tyrosine kinase [KO:K05855] [EC:2.7.10.2]
103220048  ITGB2; integrin subunit beta 2 [KO:K06464]
103220507  [KO:K05863]
103221212  PIK3CA; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha [KO:K00922] [EC:2.7.1.153]
103221595  MAPK13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
103221596  MAPK14; mitogen-activated protein kinase 14 [KO:K04441] [EC:2.7.11.24]
103221619  [KO:K11253]
103221709  AGER; advanced glycosylation end-product specific receptor [KO:K19722]
103221933  HIST1H2BO; histone cluster 1, H2bo [KO:K11252]
103221935  HIST1H2AM; histone cluster 1, H2am [KO:K11251]
103221936  [KO:K11251]
103221937  [KO:K11252]
103221938  [KO:K11254]
103221939  [KO:K11251]
103221940  [KO:K11252]
103221943  HIST1H2AL; histone cluster 1, H2al [KO:K11251]
103221945  HIST1H3J; histone H3.1-like [KO:K11253]
103221946  [KO:K11253]
103221947  [KO:K11251]
103221948  [KO:K11252]
103221968  [KO:K11251]
103221969  [KO:K11252]
103221970  [KO:K11251]
103221971  [KO:K11254]
103221972  [KO:K11252]
103221993  [KO:K11254]
103221994  [KO:K11252]
103221995  [KO:K11253]
103221996  [KO:K11252]
103221997  [KO:K11251]
103221998  [KO:K11252]
103222000  [KO:K11254]
103222001  [KO:K11252]
103222003  [KO:K11251]
103222004  [KO:K11253]
103222007  [KO:K11254]
103222008  [KO:K11254]
103222010  [KO:K11252]
103222011  [KO:K11252]
103222014  [KO:K11251]
103222015  [KO:K11252]
103222017  [KO:K11253]
103222018  [KO:K11253]
103222019  [KO:K11252]
103222030  [KO:K11252]
103222031  [KO:K11252]
103222032  [KO:K11251]
103222369  [KO:K11253]
103222373  [KO:K11253]
103222594  PIK3R1; phosphoinositide-3-kinase regulatory subunit 1 [KO:K02649]
103222941  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
103223257  NCF4; neutrophil cytosolic factor 4 [KO:K08012]
103223272  RAC2; ras-related C3 botulinum toxin substrate 2 (rho family, small GTP binding protein Rac2) [KO:K07860]
103223551  MAPK11; mitogen-activated protein kinase 11 [KO:K04441] [EC:2.7.11.24]
103223553  MAPK12; mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24]
103223554  HDAC10; histone deacetylase 10 [KO:K18671] [EC:3.5.1.98]
103223675  [KO:K06463]
103223676  FCGR2A; Fc fragment of IgG receptor IIa [KO:K06472]
103224088  [KO:K06856]
103224900  PIK3R3; phosphoinositide-3-kinase regulatory subunit 3 [KO:K02649]
103225192  HDAC1; histone deacetylase 1 [KO:K06067] [EC:3.5.1.98]
103225502  PADI4; peptidyl arginine deiminase 4 [KO:K24669]
103225615  MTOR; mechanistic target of rapamycin [KO:K07203] [EC:2.7.11.1]
103225637  PIK3CD; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta [KO:K00922] [EC:2.7.1.153]
103226127  H2AFV; H2A histone family member V [KO:K11251]
103226420  HDAC9; histone deacetylase 9 [KO:K11409] [EC:3.5.1.98]
103227249  [KO:K11252]
103227364  RELA; RELA proto-oncogene, NF-kB subunit [KO:K04735]
103227575  CAMP; cathelicidin antimicrobial peptide [KO:K13916]
103228012  ATG7; autophagy related 7 [KO:K08337]
103228031  RAF1; Raf-1 proto-oncogene, serine/threonine kinase [KO:K04366] [EC:2.7.11.1]
103228040  HDAC11; histone deacetylase 11 [KO:K11418] [EC:3.5.1.98]
103228742  CTSG; cathepsin G [KO:K01319] [EC:3.4.21.20]
103229784  AKT1; AKT serine/threonine kinase 1 [KO:K04456] [EC:2.7.11.1]
103229820  [KO:K06856]
103229828  [KO:K06856]
103229829  PRKCB; protein kinase C beta [KO:K19662] [EC:2.7.11.13]
103229838  [KO:K06856]
103229839  [KO:K06856]
103229845  [KO:K06856]
103229849  [KO:K06856]
103229850  [KO:K06856]
103229864  [KO:K06856]
103229935  [KO:K06856]
103229939  [KO:K06856]
103229942  [KO:K06856]
103229943  [KO:K06856]
103229948  [KO:K11252]
103229949  HIST3H2BB; histone cluster 3, H2bb [KO:K11252]
103229950  HIST3H2A; histone cluster 3, H2a [KO:K11251]
103229954  HIST3H3; histone cluster 3, H3 [KO:K11253]
103230172  CR1L; complement C3b/C4b receptor 1 like [KO:K04011]
103230365  [KO:K11253]
103230452  NCF2; neutrophil cytosolic factor 2 [KO:K08010]
103230532  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
103230618  SELP; selectin P [KO:K06496]
103230823  [KO:K05692]
103230869  AKT3; AKT serine/threonine kinase 3 [KO:K04456] [EC:2.7.11.1]
103231004  H3F3A; H3 histone, family 3A [KO:K11253]
103231020  CR1; complement C3b/C4b receptor 1 (Knops blood group) [KO:K04011]
103231383  ITGAM; integrin subunit alpha M [KO:K06461]
103231584  CLCN4; chloride voltage-gated channel 4 [KO:K05012]
103231601  TLR7; toll like receptor 7 [KO:K05404]
103231602  TLR8; toll like receptor 8 [KO:K10170]
103231906  ITGAL; integrin subunit alpha L [KO:K05718]
103231941  HDAC6; histone deacetylase 6 [KO:K11407] [EC:3.5.1.98]
103231978  CLCN5; chloride voltage-gated channel 5 [KO:K05012]
103232061  [KO:K11253]
103232180  HDAC8; histone deacetylase 8 [KO:K11405] [EC:3.5.1.98]
103232262  [KO:K11253]
103232425  [KO:K11252]
103232427  [KO:K11252]
103232429  [KO:K11252]
103232430  [KO:K11252]
103232431  [KO:K11252]
103232850  [KO:K11251]
103232851  [KO:K11251]
103233299  PLCB3; phospholipase C beta 3 [KO:K05858] [EC:3.1.4.11]
103233371  PLCG2; phospholipase C gamma 2 [KO:K05859] [EC:3.1.4.11]
103233451  [KO:K08009]
103233572  ELANE; elastase, neutrophil expressed [KO:K01327] [EC:3.4.21.37]
103233574  AZU1; azurocidin 1 [KO:K24665]
103233717  MAP2K2; mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
103234342  C3; complement C3 [KO:K03990]
103234391  PIK3R2; phosphoinositide-3-kinase regulatory subunit 2 [KO:K02649]
103234702  AKT2; AKT serine/threonine kinase 2 [KO:K04456] [EC:2.7.11.1]
103234937  C5AR1; complement C5a receptor 1 [KO:K04010]
103235118  SIGLEC9; sialic acid binding Ig like lectin 9 [KO:K06740]
103235144  FPR1; formyl peptide receptor 1 [KO:K04172]
103235147  FPR2; formyl peptide receptor 2 [KO:K04173]
103235155  FPR3; formyl peptide receptor 3 [KO:K04173]
103235232  PRKCG; protein kinase C gamma [KO:K19663] [EC:2.7.11.13]
103236032  [KO:K11251]
103236047  NFKB1; nuclear factor kappa B subunit 1 [KO:K02580]
103236164  [KO:K11251]
103236238  SLC25A31; solute carrier family 25 member 31 [KO:K05863]
103236415  [KO:K10159]
103236419  FGB; fibrinogen beta chain [KO:K03904]
103236420  FGA; fibrinogen alpha chain [KO:K03903]
103236421  FGG; fibrinogen gamma chain [KO:K03905]
103236517  CLCN3; chloride voltage-gated channel 3 [KO:K05012]
103236621  SLC25A4; solute carrier family 25 member 4 [KO:K05863]
103237177  [KO:K10802]
103237567  GSDMD; gasdermin D [KO:K20917]
103238208  HDAC7; histone deacetylase 7 [KO:K11408] [EC:3.5.1.98]
103239073  SELPLG; selectin P ligand [KO:K06544]
103239354  [KO:K06067] [EC:3.5.1.98]
103240115  MAP3K7; mitogen-activated protein kinase kinase kinase 7 [KO:K04427] [EC:2.7.11.25]
103240535  HDAC2; histone deacetylase 2 [KO:K06067] [EC:3.5.1.98]
103240948  [KO:K05692]
103241599  PIK3CB; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta [KO:K00922] [EC:2.7.1.153]
103242552  GP1BA; glycoprotein Ib platelet alpha subunit [KO:K06261]
103242854  MPO; myeloperoxidase [KO:K10789] [EC:1.11.2.2]
103243033  H3F3B; H3 histone, family 3B [KO:K11253]
103243171  PRKCA; protein kinase C alpha [KO:K02677] [EC:2.7.11.13]
103243277  ITGB3; integrin subunit beta 3 [KO:K06493]
103243322  ITGA2B; integrin subunit alpha 2b [KO:K06476]
103243334  HDAC5; histone deacetylase 5 [KO:K11406] [EC:3.5.1.98]
103243719  ACTG1; actin gamma 1 [KO:K05692]
103244541  VDAC1; voltage dependent anion channel 1 [KO:K05862]
103244568  H2AFY; core histone macro-H2A.1 [KO:K11251]
103244700  HDAC3; histone deacetylase 3 [KO:K11404] [EC:3.5.1.98]
103245451  MAP2K1; mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
103245558  AQP9; aquaporin 9 [KO:K09877]
103245842  PLCB2; phospholipase C beta 2 [KO:K05858] [EC:3.1.4.11]
103245987  PLCG1; phospholipase C gamma 1 [KO:K01116] [EC:3.1.4.11]
103246384  SRC; SRC proto-oncogene, non-receptor tyrosine kinase [KO:K05704] [EC:2.7.10.2]
103246591  PLCB4; phospholipase C beta 4 [KO:K05858] [EC:3.1.4.11]
103246614  NCF1; neutrophil cytosolic factor 1 [KO:K08011]
103246657  PLCB1; phospholipase C beta 1 [KO:K05858] [EC:3.1.4.11]
103246815  RAC1; ras-related C3 botulinum toxin substrate 1 (rho family, small GTP binding protein Rac1) [KO:K04392]
103246953  ACTB; actin beta [KO:K05692]
103247139  [KO:K11253]
103247163  [KO:K06498]
103247165  [KO:K11252]
103247166  [KO:K11253]
103247167  HIST2H2BE; histone cluster 2 H2B family member e [KO:K11252]
103247168  HIST2H2AC; histone cluster 2 H2A family member c [KO:K11251]
103247169  HIST2H2AB; histone cluster 2 H2A family member b [KO:K11251]
103247334  SLC25A5; solute carrier family 25 member 5 [KO:K05863]
103247374  [KO:K11253]
103247465  CYBB; cytochrome b-245 heavy chain [KO:K21421] [EC:1.-.-.-]
103247519  SLC25A6; solute carrier family 25 member 6 [KO:K05863]
103247608  [KO:K06856]
103247785  [KO:K11251]
103247786  [KO:K11253]
103247796  [KO:K11254]
103248363  [KO:K01370] [EC:3.4.22.36]
103248365  CASP1; caspase 1 [KO:K01370] [EC:3.4.22.36]
103248367  CASP4; caspase 4 [KO:K04394] [EC:3.4.22.57 3.4.22.64]
103248619  H2AFX; histone H2AX [KO:K11251]
103248933  [KO:K01370] [EC:3.4.22.36]
Compound
C00027  Hydrogen peroxide
C00039  DNA
C00076  Calcium cation
C00165  Diacylglycerol
C00338  Lipopolysaccharide
C00464  Mannan
C00518  Hyaluronate
C00551  beta-D-Glucan
C00704  Superoxide
C01245  D-myo-Inositol 1,4,5-trisphosphate
C05151  12-O-Tetradecanoylphorbol 13-acetate
C05981  Phosphatidylinositol-3,4,5-trisphosphate
C11221  Formylmethionyl-leucyl-phenylalanine methyl ester
Reference
  Authors
Van Avondt K, Hartl D
  Title
Mechanisms and disease relevance of neutrophil extracellular trap formation.
  Journal
Eur J Clin Invest 48 Suppl 2:e12919 (2018)
DOI:10.1111/eci.12919
Reference
  Authors
Sorvillo N, Cherpokova D, Martinod K, Wagner DD
  Title
Extracellular DNA NET-Works With Dire Consequences for Health.
  Journal
Circ Res 125:470-488 (2019)
DOI:10.1161/CIRCRESAHA.119.314581
Reference
  Authors
Papayannopoulos V
  Title
Neutrophil extracellular traps in immunity and disease.
  Journal
Nat Rev Immunol 18:134-147 (2018)
DOI:10.1038/nri.2017.105
Reference
  Authors
Liu FC, Chuang YH, Tsai YF, Yu HP
  Title
Role of neutrophil extracellular traps following injury.
  Journal
Shock 41:491-8 (2014)
DOI:10.1097/SHK.0000000000000146
Reference
  Authors
Yang H, Biermann MH, Brauner JM, Liu Y, Zhao Y, Herrmann M
  Title
New Insights into Neutrophil Extracellular Traps: Mechanisms of Formation and Role in Inflammation.
  Journal
Front Immunol 7:302 (2016)
DOI:10.3389/fimmu.2016.00302
Reference
  Authors
Zawrotniak M, Bochenska O, Karkowska-Kuleta J, Seweryn-Ozog K, Aoki W, Ueda M, Kozik A, Rapala-Kozik M
  Title
Aspartic Proteases and Major Cell Wall Components in Candida albicans Trigger the Release of Neutrophil Extracellular Traps.
  Journal
Front Cell Infect Microbiol 7:414 (2017)
DOI:10.3389/fcimb.2017.00414
Reference
  Authors
Honda M, Kubes P
  Title
Neutrophils and neutrophil extracellular traps in the liver and gastrointestinal system.
  Journal
Nat Rev Gastroenterol Hepatol 15:206-221 (2018)
DOI:10.1038/nrgastro.2017.183
Reference
  Authors
Hamam HJ, Palaniyar N
  Title
Post-Translational Modifications in NETosis and NETs-Mediated Diseases.
  Journal
Biomolecules 9:E369 (2019)
DOI:10.3390/biom9080369
Reference
  Authors
Burgener SS, Schroder K
  Title
Neutrophil Extracellular Traps in Host Defense.
  Journal
Cold Spring Harb Perspect Biol 12:a037028 (2020)
DOI:10.1101/cshperspect.a037028
Reference
  Authors
Vorobjeva NV, Chernyak BV
  Title
NETosis: Molecular Mechanisms, Role in Physiology and Pathology.
  Journal
Biochemistry (Mosc) 85:1178-1190 (2020)
DOI:10.1134/S0006297920100065
Reference
  Authors
Ravindran M, Khan MA, Palaniyar N
  Title
Neutrophil Extracellular Trap Formation: Physiology, Pathology, and Pharmacology.
  Journal
Biomolecules 9:E365 (2019)
DOI:10.3390/biom9080365
Reference
  Authors
Jorch SK, Kubes P
  Title
An emerging role for neutrophil extracellular traps in noninfectious disease.
  Journal
Nat Med 23:279-287 (2017)
DOI:10.1038/nm.4294
Reference
  Authors
Goggs R, Jeffery U, LeVine DN, Li RHL
  Title
Neutrophil-Extracellular Traps, Cell-Free DNA, and Immunothrombosis in Companion Animals: A Review.
  Journal
Vet Pathol 57:6-23 (2020)
DOI:10.1177/0300985819861721
Reference
  Authors
Kim SJ, Jenne CN
  Title
Role of platelets in neutrophil extracellular trap (NET) production and tissue injury.
  Journal
Semin Immunol 28:546-554 (2016)
DOI:10.1016/j.smim.2016.10.013
Reference
  Authors
de Bont CM, Boelens WC, Pruijn GJM
  Title
NETosis, complement, and coagulation: a triangular relationship.
  Journal
Cell Mol Immunol 16:19-27 (2019)
DOI:10.1038/s41423-018-0024-0
Reference
  Authors
Zawrotniak M, Bartnicka D, Rapala-Kozik M
  Title
UVA and UVB radiation induce the formation of neutrophil extracellular traps by human polymorphonuclear cells.
  Journal
J Photochem Photobiol B 196:111511 (2019)
DOI:10.1016/j.jphotobiol.2019.111511
Reference
  Authors
Remijsen Q, Kuijpers TW, Wirawan E, Lippens S, Vandenabeele P, Vanden Berghe T
  Title
Dying for a cause: NETosis, mechanisms behind an antimicrobial cell death modality.
  Journal
Cell Death Differ 18:581-8 (2011)
DOI:10.1038/cdd.2011.1
Reference
  Authors
Zawrotniak M, Rapala-Kozik M
  Title
Neutrophil extracellular traps (NETs) - formation and implications.
  Journal
Acta Biochim Pol 60:277-84 (2013)
Reference
  Authors
Rosales C
  Title
Fcgamma Receptor Heterogeneity in Leukocyte Functional Responses.
  Journal
Front Immunol 8:280 (2017)
DOI:10.3389/fimmu.2017.00280
Reference
  Authors
Vorobjeva NV, Pinegin BV
  Title
Neutrophil extracellular traps: mechanisms of formation and role in health and disease.
  Journal
Biochemistry (Mosc) 79:1286-96 (2014)
DOI:10.1134/S0006297914120025
Reference
  Authors
Delgado-Rizo V, Martinez-Guzman MA, Iniguez-Gutierrez L, Garcia-Orozco A, Alvarado-Navarro A, Fafutis-Morris M
  Title
Neutrophil Extracellular Traps and Its Implications in Inflammation: An Overview.
  Journal
Front Immunol 8:81 (2017)
DOI:10.3389/fimmu.2017.00081
Reference
  Authors
Fonseca Z, Diaz-Godinez C, Mora N, Aleman OR, Uribe-Querol E, Carrero JC, Rosales C
  Title
Entamoeba histolytica Induce Signaling via Raf/MEK/ERK for Neutrophil Extracellular Trap (NET) Formation.
  Journal
Front Cell Infect Microbiol 8:226 (2018)
DOI:10.3389/fcimb.2018.00226
Reference
  Authors
Agraz-Cibrian JM, Giraldo DM, Mary FM, Urcuqui-Inchima S
  Title
Understanding the molecular mechanisms of NETs and their role in antiviral innate immunity.
  Journal
Virus Res 228:124-133 (2017)
DOI:10.1016/j.virusres.2016.11.033
Reference
  Authors
Schonrich G, Raftery MJ
  Title
Neutrophil Extracellular Traps Go Viral.
  Journal
Front Immunol 7:366 (2016)
DOI:10.3389/fimmu.2016.00366
Reference
  Authors
Saitoh T, Komano J, Saitoh Y, Misawa T, Takahama M, Kozaki T, Uehata T, Iwasaki H, Omori H, Yamaoka S, Yamamoto N, Akira S
  Title
Neutrophil extracellular traps mediate a host defense response to human immunodeficiency virus-1.
  Journal
Cell Host Microbe 12:109-16 (2012)
DOI:10.1016/j.chom.2012.05.015
Reference
  Authors
Kumar S, Gupta E, Kaushik S, Jyoti A
  Title
Neutrophil Extracellular Traps: Formation and Involvement in Disease Progression.
  Journal
Iran J Allergy Asthma Immunol 17:208-220 (2018)
Related
pathway
csab04010  MAPK signaling pathway
csab04020  Calcium signaling pathway
csab04140  Autophagy - animal
csab04151  PI3K-Akt signaling pathway
csab04610  Complement and coagulation cascades
csab04611  Platelet activation
csab04620  Toll-like receptor signaling pathway
csab04621  NOD-like receptor signaling pathway
csab04666  Fc gamma R-mediated phagocytosis
KO pathway
ko04613   

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