KEGG   PATHWAY: pcoo04613
Entry
pcoo04613                   Pathway                                
Name
Neutrophil extracellular trap formation - Puma concolor (puma)
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
pcoo04613  Neutrophil extracellular trap formation
pcoo04613

Organism
Puma concolor (puma) [GN:pcoo]
Gene
112864824  low affinity immunoglobulin gamma Fc region receptor III-like isoform X1 [KO:K06463]
112868539  SYK; tyrosine-protein kinase SYK [KO:K05855] [EC:2.7.10.2]
112861992  MAP3K7; mitogen-activated protein kinase kinase kinase 7 isoform X1 [KO:K04427] [EC:2.7.11.25]
112859466  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
112855545  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
112852828  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
112856394  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
112870302  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
112871449  cytochrome b-245 heavy chain [KO:K21421] [EC:1.-.-.-]
112859882  NCF1; neutrophil cytosol factor 1 [KO:K08011]
112857529  cytochrome b-245 light chain [KO:K08009]
112857631  NCF2; neutrophil cytosol factor 2 isoform X1 [KO:K08010]
112863350  NCF4; neutrophil cytosol factor 4 [KO:K08012]
112859959  RAC1; ras-related C3 botulinum toxin substrate 1 [KO:K04392]
112863355  RAC2; ras-related C3 botulinum toxin substrate 2 [KO:K07860]
112871667  TLR7; toll-like receptor 7 [KO:K05404]
112871637  TLR8; toll-like receptor 8 [KO:K10170]
112855538  myeloperoxidase [KO:K10789] [EC:1.11.2.2]
112864619  ACTG1; actin, cytoplasmic 2 [KO:K05692]
112860092  ACTB; actin, cytoplasmic 1 [KO:K05692]
112861387  VDAC1; LOW QUALITY PROTEIN: voltage-dependent anion-selective channel protein 1 [KO:K05862]
112854800  VDAC2; voltage-dependent anion-selective channel protein 2 [KO:K15040]
112858617  VDAC3; voltage-dependent anion-selective channel protein 3 isoform X1 [KO:K15041]
112869897  SLC25A4; ADP/ATP translocase 1 [KO:K05863]
112870821  SLC25A5; ADP/ATP translocase 2 [KO:K05863]
112858372  SLC25A31; ADP/ATP translocase 4 [KO:K05863]
112871659  SLC25A6; ADP/ATP translocase 3 isoform X1 [KO:K05863]
112854251  PPIF; peptidyl-prolyl cis-trans isomerase F, mitochondrial [KO:K09565] [EC:5.2.1.8]
112862006  protein-arginine deiminase type-4-like [KO:K24669] [EC:3.5.3.15]
112872287  FCGR1A; high affinity immunoglobulin gamma Fc receptor I isoform X1 [KO:K06498]
112856162  integrin alpha-M-like [KO:K06461]
112849420  ITGB2; integrin beta-2 [KO:K06464]
112856284  ITGAL; integrin alpha-L [KO:K05718]
112867756  CLEC7A; C-type lectin domain family 7 member A isoform X1 [KO:K10074]
112869273  SRC; proto-oncogene tyrosine-protein kinase Src [KO:K05704] [EC:2.7.10.2]
112855622  PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 [KO:K05858] [EC:3.1.4.11]
112869362  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 [KO:K05858] [EC:3.1.4.11]
112869587  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 [KO:K05858] [EC:3.1.4.11]
112851908  PLCB3; LOW QUALITY PROTEIN: 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 [KO:K05858] [EC:3.1.4.11]
112869500  PLCG1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 [KO:K01116] [EC:3.1.4.11]
112857487  PLCG2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2 [KO:K05859] [EC:3.1.4.11]
112864470  PRKCA; LOW QUALITY PROTEIN: protein kinase C alpha type [KO:K02677] [EC:2.7.11.13]
112853117  PRKCB; protein kinase C beta type [KO:K19662] [EC:2.7.11.13]
112850908  PRKCG; protein kinase C gamma type [KO:K19663] [EC:2.7.11.13]
112857913  ATG7; ubiquitin-like modifier-activating enzyme ATG7 [KO:K08337]
112851194  FPR2; N-formyl peptide receptor 2 [KO:K04173]
112849397  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
112849524  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
112848856  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:2.7.1.153]
112861619  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
112868847  phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649]
112863208  AKT3; RAC-gamma serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
112851313  AKT2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
112848905  MTOR; serine/threonine-protein kinase mTOR [KO:K07203] [EC:2.7.11.1]
112858048  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
112851941  RELA; transcription factor p65 [KO:K04735]
112857686  CR1; complement receptor type 1 [KO:K04011]
112865031  C5; complement C5 [KO:K03994]
112851164  C5AR1; C5a anaphylatoxin chemotactic receptor 1 [KO:K04010]
112861121  HMGB1; high mobility group protein B1 [KO:K10802]
112858853  toll-like receptor 2 [KO:K10159]
112860159  TLR4; toll-like receptor 4 [KO:K10160]
112862836  MAPK13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
112862837  MAPK14; mitogen-activated protein kinase 14 [KO:K04441] [EC:2.7.11.24]
112863384  MAPK12; mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24]
112853975  ITGA2B; LOW QUALITY PROTEIN: integrin alpha-IIb [KO:K06476]
112862191  ITGB3; LOW QUALITY PROTEIN: integrin beta-3 [KO:K06493]
112858552  FGA; fibrinogen alpha chain [KO:K03903]
112858467  FGB; fibrinogen beta chain [KO:K03904]
112858317  FGG; fibrinogen gamma chain [KO:K03905]
112867211  VWF; von Willebrand factor [KO:K03900]
112863109  SELP; P-selectin [KO:K06496]
112870456  SELPLG; LOW QUALITY PROTEIN: P-selectin glycoprotein ligand 1 [KO:K06544]
112853779  AGER; advanced glycosylation end product-specific receptor [KO:K19722]
112866024  caspase-1 isoform X1 [KO:K04394] [EC:3.4.22.57 3.4.22.64]
112871765  HAT1; histone acetyltransferase type B catalytic subunit [KO:K11303] [EC:2.3.1.48]
112856821  histone H2A type 3 [KO:K11251]
112864871  histone H2A-Bbd type 1-like [KO:K11251]
112865118  histone H2AX [KO:K11251]
112872181  histone H2B type 2-E-like [KO:K11251]
112872182  histone H2A type 2-C [KO:K11251]
112866290  histone H2A-Bbd type 2/3-like [KO:K11251]
112853467  histone H2A type 1-C [KO:K11251]
112853468  histone H2A type 1-E [KO:K11251]
112853469  histone H2A type 1-E [KO:K11251]
112853470  histone H2A type 1-H-like [KO:K11251]
112853471  histone H2A type 1-B/E [KO:K11251]
112853472  histone H2A type 1-B/E isoform X1 [KO:K11251]
112853473  histone H2A type 1-E-like [KO:K11251]
112853495  histone H2A type 1-B/E [KO:K11251]
112853508  histone H2A-IV-like [KO:K11251]
112860110  histone H2A.V [KO:K11251]
112854394  core histone macro-H2A.2 [KO:K11251]
112861289  core histone macro-H2A.1 isoform X1 [KO:K11251]
112867718  histone H2A.J [KO:K11251]
112861707  histone H2B subacrosomal variant-like [KO:K11252]
112868759  histone H2B type 2-F [KO:K11252]
112856933  histone H2B type 3-B [KO:K11252]
112853475  histone H2B type 1 [KO:K11252]
112853476  histone H2B type 1 [KO:K11252]
112853477  histone H2B type 1 [KO:K11252]
112853478  histone H2B type 1-J [KO:K11252]
112853479  histone H2B type 1 [KO:K11252]
112853480  histone H2B type 1 [KO:K11252]
112853481  histone H2B type 1-K [KO:K11252]
112853482  histone H2B type 1-M [KO:K11252]
112853484  histone H2B type 1-K [KO:K11252]
112853485  histone H2B type 1-B [KO:K11252]
112853486  histone H2B type 1-K-like [KO:K11252]
112853496  histone H2B type 1 [KO:K11252]
112853498  histone H2B type 1-A-like [KO:K11252]
112853672  histone H2B type 1-A [KO:K11252]
112853774  uncharacterized protein LOC112853774 [KO:K11254]
112863142  histone H3.3 [KO:K11253]
112856894  LOW QUALITY PROTEIN: histone H3.3 [KO:K11253]
112853454  uncharacterized protein LOC112853454 isoform X1 [KO:K11253]
112853465  histone H3.1 [KO:K11253]
112853466  histone H3.1 [KO:K11253]
112853491  histone H3.1 [KO:K11253]
112853492  histone H3.1 [KO:K11253]
112853493  histone H3.1-like [KO:K11253]
112868534  HDAC1; histone deacetylase 1 isoform X1 [KO:K06067] [EC:3.5.1.98]
112862527  HDAC2; histone deacetylase 2 [KO:K06067] [EC:3.5.1.98]
112860215  HDAC3; histone deacetylase 3 isoform X1 [KO:K11404] [EC:3.5.1.98]
112854066  HDAC5; LOW QUALITY PROTEIN: histone deacetylase 5 [KO:K11406] [EC:3.5.1.98]
112867663  HDAC4; LOW QUALITY PROTEIN: histone deacetylase 4 [KO:K11406] [EC:3.5.1.98]
112870931  HDAC6; histone deacetylase 6 [KO:K11407] [EC:3.5.1.98]
112867518  HDAC7; histone deacetylase 7 [KO:K11408] [EC:3.5.1.98]
112870833  HDAC8; histone deacetylase 8 isoform X1 [KO:K11405] [EC:3.5.1.98]
112866556  HDAC9; histone deacetylase 9 isoform X1 [KO:K11409] [EC:3.5.1.98]
112858854  HDAC11; histone deacetylase 11 isoform X1 [KO:K11418] [EC:3.5.1.98]
112855266  cathepsin G-like [KO:K01319] [EC:3.4.21.20]
112852707  CAMP; cathelicidin antimicrobial peptide [KO:K13916]
112870817  CLCN5; H(+)/Cl(-) exchange transporter 5 isoform X1 [KO:K05012]
112858115  CLCN3; H(+)/Cl(-) exchange transporter 3 isoform X1 [KO:K05012]
112871700  CLCN4; H(+)/Cl(-) exchange transporter 4 isoform X1 [KO:K05012]
112856501  AQP9; aquaporin-9 [KO:K09877]
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:E369 (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:E365 (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
pcoo04010  MAPK signaling pathway
pcoo04020  Calcium signaling pathway
pcoo04140  Autophagy - animal
pcoo04151  PI3K-Akt signaling pathway
pcoo04610  Complement and coagulation cascades
pcoo04611  Platelet activation
pcoo04620  Toll-like receptor signaling pathway
pcoo04621  NOD-like receptor signaling pathway
pcoo04666  Fc gamma R-mediated phagocytosis
KO pathway
ko04613   
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