KEGG   PATHWAY: pvp04613
Entry
pvp04613                    Pathway                                
Name
Neutrophil extracellular trap formation - Pteropus vampyrus (large flying fox)
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
pvp04613  Neutrophil extracellular trap formation
pvp04613

Organism
Pteropus vampyrus (large flying fox) [GN:pvp]
Gene
105288306  NCF4; neutrophil cytosol factor 4 [KO:K08012]
105288781  PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 [KO:K05858] [EC:3.1.4.11]
105288878  VDAC2; voltage-dependent anion-selective channel protein 2 [KO:K15040]
105288974  PPIF; peptidyl-prolyl cis-trans isomerase F, mitochondrial [KO:K09565] [EC:5.2.1.8]
105289326  MAPK1; mitogen-activated protein kinase 1 isoform X2 [KO:K04371] [EC:2.7.11.24]
105289863  PLCG2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2 [KO:K05859] [EC:3.1.4.11]
105290446  HAT1; histone acetyltransferase type B catalytic subunit isoform X2 [KO:K11303] [EC:2.3.1.48]
105290575  HDAC1; histone deacetylase 1 [KO:K06067] [EC:3.5.1.98]
105291526  TLR2; toll-like receptor 2 [KO:K10159]
105291761  GP1BA; platelet glycoprotein Ib alpha chain [KO:K06261]
105291893  [KO:K11253]
105292095  HMGB1; high mobility group protein B1 [KO:K10802]
105292161  CLCN3; H(+)/Cl(-) exchange transporter 3 isoform X3 [KO:K05012]
105292188  FGB; fibrinogen beta chain [KO:K03904]
105292189  FGG; fibrinogen gamma chain isoform X1 [KO:K03905]
105292224  FGA; fibrinogen alpha chain [KO:K03903]
105292582  [KO:K11253]
105292652  TLR4; toll-like receptor 4 [KO:K10160]
105292665  C5; complement C5 [KO:K03994]
105293029  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
105293361  [KO:K11253]
105293469  SLC25A31; ADP/ATP translocase 4 [KO:K05863]
105293587  [KO:K11251]
105293648  VDAC1; voltage-dependent anion-selective channel protein 1 [KO:K05862]
105293974  CLCN4; H(+)/Cl(-) exchange transporter 4 [KO:K05012]
105293980  TLR7; toll-like receptor 7 [KO:K05404]
105293981  TLR8; toll-like receptor 8 [KO:K10170]
105294324  AQP9; aquaporin-9 isoform X1 [KO:K09877]
105294397  PADI4; protein-arginine deiminase type-4 [KO:K24669]
105294429  MTOR; serine/threonine-protein kinase mTOR [KO:K07203] [EC:2.7.11.1]
105294565  ACTB; actin, cytoplasmic 1 isoform X1 [KO:K05692]
105294623  RAC1; LOW QUALITY PROTEIN: ras-related C3 botulinum toxin substrate 1 [KO:K04392]
105294703  SLC25A4; ADP/ATP translocase 1 [KO:K05863]
105294980  HDAC11; histone deacetylase 11 isoform X1 [KO:K11418] [EC:3.5.1.98]
105295022  HDAC9; histone deacetylase 9 [KO:K11409] [EC:3.5.1.98]
105295040  NCF2; neutrophil cytosol factor 2 [KO:K08010]
105295257  HDAC2; histone deacetylase 2 [KO:K06067] [EC:3.5.1.98]
105295516  [KO:K05863]
105295897  CLEC7A; C-type lectin domain family 7 member A isoform X1 [KO:K10074]
105296024  VWF; von Willebrand factor [KO:K03900]
105296302  [KO:K11251]
105296305  [KO:K11252]
105296306  [KO:K11252]
105296307  [KO:K11254]
105296308  [KO:K11251]
105296310  [KO:K11253]
105296311  [KO:K11254]
105296318  [KO:K11252]
105296321  [KO:K11251]
105296322  [KO:K11251]
105296327  [KO:K11252]
105296328  [KO:K11251]
105296402  [KO:K11253]
105296513  SRC; proto-oncogene tyrosine-protein kinase Src [KO:K05704] [EC:2.7.10.2]
105296521  PLCG1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 [KO:K01116] [EC:3.1.4.11]
105296605  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
105297002  MAP3K7; mitogen-activated protein kinase kinase kinase 7 [KO:K04427] [EC:2.7.11.25]
105297029  HDAC3; histone deacetylase 3 [KO:K11404] [EC:3.5.1.98]
105297140  [KO:K02649]
105297312  C5AR1; C5a anaphylatoxin chemotactic receptor 1 [KO:K04010]
105297443  [KO:K04394] [EC:3.4.22.57 3.4.22.64]
105297444  CASP1; caspase-1 isoform X1 [KO:K01370] [EC:3.4.22.36]
105297474  [KO:K04394] [EC:3.4.22.57 3.4.22.64]
105297500  HDAC7; histone deacetylase 7 isoform X1 [KO:K11408] [EC:3.5.1.98]
105297702  PRKCA; protein kinase C alpha type isoform X1 [KO:K02677] [EC:2.7.11.13]
105297846  PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 [KO:K05858] [EC:3.1.4.11]
105297999  RELA; transcription factor p65 [KO:K04735]
105298702  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
105298737  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X1 [KO:K05858] [EC:3.1.4.11]
105299021  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
105299027  ATG7; ubiquitin-like modifier-activating enzyme ATG7 isoform X2 [KO:K08337]
105299371  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X3 [KO:K02649]
105299444  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 [KO:K05858] [EC:3.1.4.11]
105299667  NCF1; neutrophil cytosol factor 1 isoform X1 [KO:K08011]
105299771  [KO:K11251]
105299832  SELP; LOW QUALITY PROTEIN: P-selectin [KO:K06496]
105299919  [KO:K08009]
105299948  [KO:K11253]
105299998  [KO:K11251]
105300115  [KO:K11251]
105300159  [KO:K04456] [EC:2.7.11.1]
105300248  SYK; tyrosine-protein kinase SYK isoform X1 [KO:K05855] [EC:2.7.10.2]
105300538  VDAC3; voltage-dependent anion-selective channel protein 3 isoform X1 [KO:K15041]
105301035  MAPK14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
105301036  MAPK13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
105301109  C3; complement C3 [KO:K03990]
105301152  ACTG1; actin, cytoplasmic 2 [KO:K05692]
105301988  GSDMD; gasdermin-D [KO:K20917]
105302124  MPO; myeloperoxidase [KO:K10789] [EC:1.11.2.2]
105302515  [KO:K11251]
105302777  [KO:K11251]
105302803  [KO:K11254]
105303028  ITGB2; integrin beta-2 [KO:K06464]
105303404  [KO:K06463]
105303446  ITGB3; integrin beta-3 isoform X1 [KO:K06493]
105303496  HDAC5; histone deacetylase 5 isoform X1 [KO:K11406] [EC:3.5.1.98]
105303529  ITGA2B; integrin alpha-IIb [KO:K06476]
105303775  [KO:K11252]
105303899  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
105303938  SELPLG; P-selectin glycoprotein ligand 1 [KO:K06544]
105304501  ITGAM; integrin alpha-M isoform X1 [KO:K06461]
105304532  ITGAL; integrin alpha-L isoform X1 [KO:K05718]
105304566  MAPK3; mitogen-activated protein kinase 3 isoform X1 [KO:K04371] [EC:2.7.11.24]
105305213  [KO:K11406] [EC:3.5.1.98]
105305278  AGER; advanced glycosylation end product-specific receptor isoform X9 [KO:K19722]
105305546  SLC25A5; ADP/ATP translocase 2 [KO:K05863]
105306588  [KO:K04173]
105306744  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
105307067  [KO:K11253]
105307215  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
105307575  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
105307757  HDAC8; histone deacetylase 8 isoform X1 [KO:K11405] [EC:3.5.1.98]
105308002  [KO:K05863]
105308283  [KO:K04441] [EC:2.7.11.24]
105308284  HDAC10; histone deacetylase 10 isoform X2 [KO:K18671] [EC:3.5.1.98]
105308561  [KO:K21421] [EC:1.-.-.-]
105308687  [KO:K11252]
105308756  [KO:K11251]
105308818  [KO:K19662] [EC:2.7.11.13]
105308856  [KO:K11251]
105308956  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X2 [KO:K00922] [EC:2.7.1.153]
105309239  [KO:K11251]
105309409  [KO:K01319] [EC:3.4.21.20]
105309413  [KO:K01319] [EC:3.4.21.20]
105309462  PRKCG; protein kinase C gamma type [KO:K19663] [EC:2.7.11.13]
105309827  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 isoform X1 [KO:K04368] [EC:2.7.12.2]
105309965  CLCN5; H(+)/Cl(-) exchange transporter 5 isoform X1 [KO:K05012]
105309973  [KO:K06498]
105309974  [KO:K11252]
105309975  [KO:K11251]
105309976  [KO:K11253]
105309978  [KO:K11252]
105310009  HDAC6; histone deacetylase 6 isoform X2 [KO:K11407] [EC:3.5.1.98]
105310426  [KO:K08012]
105310606  [KO:K11252]
105310940  [KO:K04173]
105311102  [KO:K11251]
105311111  [KO:K11252]
105311488  [KO:K11252]
105311489  [KO:K11252]
105311490  [KO:K11252]
105311491  [KO:K11252]
105311492  [KO:K11252]
105311532  RAC2; ras-related C3 botulinum toxin substrate 2 isoform X2 [KO:K07860]
105311720  [KO:K11252]
105311756  [KO:K11252]
105311769  [KO:K11252]
111728728  [KO:K11251]
111728749  [KO:K11251]
111739453  [KO:K11252]
111743863  [KO:K11251]
111743870  [KO:K11254]
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
PMID:29543328
  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
PMID:31518165
  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
PMID:28990587
  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
PMID:24837201
  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
PMID:27570525
  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
PMID:28983472
  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
PMID:29382950
  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
PMID:31416265
  Authors
Hamam HJ, Palaniyar N
  Title
Post-Translational Modifications in NETosis and NETs-Mediated Diseases.
  Journal
Biomolecules 9:369 (2019)
DOI:10.3390/biom9080369
Reference
PMID:31767647
  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
PMID:33202203
  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
PMID:31416173
  Authors
Ravindran M, Khan MA, Palaniyar N
  Title
Neutrophil Extracellular Trap Formation: Physiology, Pathology, and Pharmacology.
  Journal
Biomolecules 9:365 (2019)
DOI:10.3390/biom9080365
Reference
PMID:28267716
  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
PMID:31342866
  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
PMID:27876233
  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
PMID:29572545
  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
PMID:31129510
  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
PMID:21293492
  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
PMID:23819131
  Authors
Zawrotniak M, Rapala-Kozik M
  Title
Neutrophil extracellular traps (NETs) - formation and implications.
  Journal
Acta Biochim Pol 60:277-84 (2013)
Reference
PMID:28373871
  Authors
Rosales C
  Title
Fcgamma Receptor Heterogeneity in Leukocyte Functional Responses.
  Journal
Front Immunol 8:280 (2017)
DOI:10.3389/fimmu.2017.00280
Reference
PMID:25716722
  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
PMID:28220120
  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
PMID:30023352
  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
PMID:27923601
  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
PMID:27698656
  Authors
Schonrich G, Raftery MJ
  Title
Neutrophil Extracellular Traps Go Viral.
  Journal
Front Immunol 7:366 (2016)
DOI:10.3389/fimmu.2016.00366
Reference
PMID:22817992
  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
PMID:29908538
  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
pvp04010  MAPK signaling pathway
pvp04020  Calcium signaling pathway
pvp04140  Autophagy - animal
pvp04151  PI3K-Akt signaling pathway
pvp04610  Complement and coagulation cascades
pvp04611  Platelet activation
pvp04620  Toll-like receptor signaling pathway
pvp04621  NOD-like receptor signaling pathway
pvp04666  Fc gamma R-mediated phagocytosis
KO pathway
ko04613   

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