KEGG   PATHWAY: aju04613
Entry
aju04613                    Pathway                                
Name
Neutrophil extracellular trap formation - Acinonyx jubatus (cheetah)
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
aju04613  Neutrophil extracellular trap formation
aju04613

Organism
Acinonyx jubatus (cheetah) [GN:aju]
Gene
106986773  low affinity immunoglobulin gamma Fc region receptor III-A isoform X1 [KO:K06463]
106976132  tyrosine-protein kinase SYK isoform X1 [KO:K05855] [EC:2.7.10.2]
106983077  mitogen-activated protein kinase kinase kinase 7 isoform X1 [KO:K04427] [EC:2.7.11.25]
106977129  RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
106980282  dual specificity mitogen-activated protein kinase kinase 1 isoform X2 [KO:K04368] [EC:2.7.12.2]
106975474  dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
106969232  mitogen-activated protein kinase 3 isoform X2 [KO:K04371] [EC:2.7.11.24]
106990008  mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
106982016  cytochrome b-245 heavy chain [KO:K21421] [EC:1.-.-.-]
106977527  neutrophil cytosol factor 1 isoform X1 [KO:K08011]
113604395  cytochrome b-245 light chain [KO:K08009]
106975923  neutrophil cytosol factor 2 isoform X1 [KO:K08010]
106981033  neutrophil cytosol factor 4 isoform X1 [KO:K08012]
106982604  ras-related C3 botulinum toxin substrate 1 isoform X2 [KO:K04392]
106981077  ras-related C3 botulinum toxin substrate 2 isoform X1 [KO:K07860]
106971060  toll-like receptor 7 isoform X1 [KO:K05404]
106971061  toll-like receptor 8 isoform X2 [KO:K10170]
113597259  neutrophil elastase-like isoform X1 [KO:K01327] [EC:3.4.21.37]
106989943  myeloperoxidase isoform X2 [KO:K10789] [EC:1.11.2.2]
106987399  actin, cytoplasmic 2 [KO:K05692]
106984514  actin, cytoplasmic 1 [KO:K05692]
106984918  voltage-dependent anion-selective channel protein 1 [KO:K05862]
106969683  voltage-dependent anion-selective channel protein 2 [KO:K15040]
106990014  voltage-dependent anion-selective channel protein 3 [KO:K15041]
106976249  voltage-dependent anion-selective channel protein 3-like [KO:K15041]
106970551  LOW QUALITY PROTEIN: ADP/ATP translocase 2-like [KO:K05863]
106970899  ADP/ATP translocase 2 [KO:K05863]
106982226  ADP/ATP translocase 1 [KO:K05863]
106982044  ADP/ATP translocase 3 [KO:K05863]
106988175  ADP/ATP translocase 4 [KO:K05863]
106969697  peptidyl-prolyl cis-trans isomerase F, mitochondrial isoform X1 [KO:K09565] [EC:5.2.1.8]
106975589  protein-arginine deiminase type-4 [KO:K24669] [EC:3.5.3.15]
106982107  LOW QUALITY PROTEIN: high affinity immunoglobulin gamma Fc receptor I [KO:K06498]
106979120  integrin alpha-M isoform X1 [KO:K06461]
106985666  integrin beta-2 [KO:K06464]
106979092  integrin alpha-L isoform X3 [KO:K05718]
106965717  C-type lectin domain family 7 member A isoform X1 [KO:K10074]
106974507  proto-oncogene tyrosine-protein kinase Src isoform X1 [KO:K05704] [EC:2.7.10.2]
106976431  1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X1 [KO:K05858] [EC:3.1.4.11]
106976432  1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 isoform X1 [KO:K05858] [EC:3.1.4.11]
106981698  1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 isoform X1 [KO:K05858] [EC:3.1.4.11]
106968579  1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 isoform X1 [KO:K05858] [EC:3.1.4.11]
106974495  1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 isoform X1 [KO:K01116] [EC:3.1.4.11]
106984018  1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2 isoform X1 [KO:K05859] [EC:3.1.4.11]
106975306  protein kinase C alpha type isoform X1 [KO:K02677] [EC:2.7.11.13]
106970449  protein kinase C beta type isoform X1 [KO:K19662] [EC:2.7.11.13]
106980855  protein kinase C gamma type isoform X1 [KO:K19663] [EC:2.7.11.13]
106977116  ubiquitin-like modifier-activating enzyme ATG7 isoform X1 [KO:K08337]
106973011  N-formyl peptide receptor 2 [KO:K04173]
106984896  phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
106984265  phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
106973880  phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
106976917  phosphatidylinositol 3-kinase regulatory subunit alpha isoform X2 [KO:K02649]
106973297  LOW QUALITY PROTEIN: phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
106969150  phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
106979622  RAC-beta serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
106975558  RAC-gamma serine/threonine-protein kinase isoform X2 [KO:K04456] [EC:2.7.11.1]
106985046  RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
106984907  serine/threonine-protein kinase mTOR isoform X2 [KO:K07203] [EC:2.7.11.1]
106984704  nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
106971136  transcription factor p65 [KO:K04735]
128314961  complement C3-like [KO:K03990]
128314963  complement C3-like isoform X1 [KO:K03990]
106975430  complement C3 [KO:K03990]
106981814  complement component receptor 1-like protein isoform X2 [KO:K04011]
106986632  complement C5 [KO:K03994]
106973630  C5a anaphylatoxin chemotactic receptor 1 isoform X1 [KO:K04010]
113593044  LOW QUALITY PROTEIN: high mobility group protein B1-like [KO:K10802]
106985545  high mobility group protein B1 [KO:K10802]
106982476  toll-like receptor 2 [KO:K10159]
106977278  toll-like receptor 4 isoform X1 [KO:K10160]
106972806  mitogen-activated protein kinase 13 isoform X1 [KO:K04441] [EC:2.7.11.24]
106987636  mitogen-activated protein kinase 12 isoform X1 [KO:K04441] [EC:2.7.11.24]
106987637  mitogen-activated protein kinase 11 isoform X1 [KO:K04441] [EC:2.7.11.24]
106972759  mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
106974321  integrin alpha-IIb [KO:K06476]
106988847  integrin beta-3 [KO:K06493]
106982472  fibrinogen alpha chain [KO:K03903]
106982473  fibrinogen beta chain [KO:K03904]
106982471  fibrinogen gamma chain [KO:K03905]
106972394  platelet glycoprotein Ib alpha chain [KO:K06261]
106965451  von Willebrand factor [KO:K03900]
106966205  P-selectin isoform X2 [KO:K06496]
106978238  P-selectin glycoprotein ligand 1 isoform X1 [KO:K06544]
106983491  advanced glycosylation end product-specific receptor isoform X4 [KO:K19722]
106976501  caspase-1 isoform X1 [KO:K04394] [EC:3.4.22.57 3.4.22.64]
106981485  gasdermin-D [KO:K20917]
106987902  histone acetyltransferase type B catalytic subunit [KO:K11303] [EC:2.3.1.48]
128311497  histone H2A-Bbd type 2/3-like [KO:K11251]
128313973  histone H2A type 2-A [KO:K11251]
128315723  histone H2A type 1-B [KO:K11251]
128315724  histone H2A type 1-E [KO:K11251]
128315725  histone H2A type 1-H-like [KO:K11251]
128315747  histone H2A type 1-E [KO:K11251]
106968229  histone H2A.V isoform X2 [KO:K11251]
106967157  core histone macro-H2A.2 [KO:K11251]
106965661  histone H2A.J [KO:K11251]
106989149  core histone macro-H2A.1 isoform X1 [KO:K11251]
106988025  histone H2A type 1-E-like [KO:K11251]
106988033  histone H2A type 2-A [KO:K11251]
106988039  histone H2A type 1-C [KO:K11251]
106988045  histone H2A-beta, sperm-like [KO:K11251]
106988058  histone H2A type 1-B [KO:K11251]
106985217  histone H2A type 3 [KO:K11251]
106978991  histone H2A.Z [KO:K11251]
106989769  histone H2A-beta, sperm-like [KO:K11251]
106976312  histone H2A type 1-E [KO:K11251]
106976318  histone H2A type 1-E-like [KO:K11251]
106976324  histone H2A type 1-J [KO:K11251]
113597355  histone H2A-Bbd type 2/3 [KO:K11251]
113597356  histone H2A-Bbd type 2/3 [KO:K11251]
106986678  histone H2A type 2-B [KO:K11251]
113597922  histone H2A type 2-C [KO:K11251]
113598029  histone H2A-beta, sperm-like [KO:K11251]
113593208  histone H2AX [KO:K11251]
106989349  histone H2A-IV [KO:K11251]
113593972  histone H2A type 1-E-like [KO:K11251]
106988070  histone H2A type 1-H-like [KO:K11251]
106988057  histone H2A type 1-B [KO:K11251]
106976326  histone H2A type 1-E [KO:K11251]
106988063  histone H2B type 1-C/E/F/G/I [KO:K11252]
128313974  histone H2B type 2-E-like [KO:K11252]
128313981  histone H2B type 2-E-like [KO:K11252]
128315726  histone H2B type 1-M [KO:K11252]
128315728  histone H2B type 1-B [KO:K11252]
128315729  histone H2B type 1-C/E/F/G/I [KO:K11252]
128315730  histone H2B type 1-K-like [KO:K11252]
128315731  histone H2B type 1-C/E/F/G/I [KO:K11252]
128315732  histone H2B type 1-C/E/F/G/I [KO:K11252]
128315748  histone H2B type 1-C/E/F/G/I [KO:K11252]
106969569  histone H2B type 2-K1 [KO:K11252]
106988040  histone H2B type 1-C/E/F/G/I [KO:K11252]
106988062  histone H2B type 1-M [KO:K11252]
106988064  histone H2B type 1-K [KO:K11252]
106988066  histone H2B type 1-C/E/F/G/I [KO:K11252]
106988082  histone H2B type 1-A-like [KO:K11252]
106974815  histone H2B subacrosomal variant-like [KO:K11252]
106989350  histone H2B type 1-A [KO:K11252]
106985218  histone H2B type 3-B [KO:K11252]
106986679  histone H2B type 2-E [KO:K11252]
106982106  histone H2B type 2-F [KO:K11252]
106976313  histone H2B type 1-K [KO:K11252]
106985210  LOW QUALITY PROTEIN: uncharacterized protein LOC106985210 [KO:K11252]
113597270  histone H2B type 1-C/E/F/G/I [KO:K11252]
113592690  histone H2A.N [KO:K11252]
113593971  histone H2B type 1-C/E/F/G/I [KO:K11252]
106988080  histone H2B type 1-J [KO:K11252]
128315721  histone H2B type 1-C/E/F/G/I-like [KO:K11252]
106965662  uncharacterized protein LOC106965662 isoform X1 [KO:K11254]
106988031  histone H4 [KO:K11254]
106988053  histone H4 [KO:K11254]
106988073  histone H4 [KO:K11254]
106988075  histone H4 [KO:K11254]
106988077  histone H4 [KO:K11254]
106982111  histone H4 [KO:K11254]
106976329  histone H4 [KO:K11254]
106988032  histone H4 [KO:K11254]
113593855  histone H4 [KO:K11254]
128315790  uncharacterized protein LOC128315790 [KO:K11253]
128315791  uncharacterized protein LOC128315791 [KO:K11253]
106968593  histone H3.3A [KO:K11253]
106988026  uncharacterized protein LOC106988026 [KO:K11253]
106988055  histone H3.1 [KO:K11253]
106985220  H3-4; LOW QUALITY PROTEIN: histone H3.1t [KO:K11253]
106974444  histone H3.3A-like [KO:K11253]
106987747  histone H3.3A [KO:K11253]
113597382  histone H3-like [KO:K11253]
113593970  histone H3.1 [KO:K11253]
113593854  LOW QUALITY PROTEIN: uncharacterized protein LOC113593854 [KO:K11253]
106988076  histone H3.1 [KO:K11253]
106968918  histone deacetylase 2 isoform X1 [KO:K06067] [EC:3.5.1.98]
106982428  histone deacetylase 1 isoform X1 [KO:K06067] [EC:3.5.1.98]
106967267  histone deacetylase 3 isoform X1 [KO:K11404] [EC:3.5.1.98]
106967107  histone deacetylase 4 isoform X1 [KO:K11406] [EC:3.5.1.98]
106974278  histone deacetylase 5 isoform X1 [KO:K11406] [EC:3.5.1.98]
106989010  histone deacetylase 6 isoform X1 [KO:K11407] [EC:3.5.1.98]
106969353  histone deacetylase 7 isoform X1 [KO:K11408] [EC:3.5.1.98]
106982392  histone deacetylase 8 isoform X8 [KO:K11405] [EC:3.5.1.98]
106984149  histone deacetylase 9 isoform X1 [KO:K11409] [EC:3.5.1.98]
106987623  polyamine deacetylase HDAC10 isoform X3 [KO:K18671] [EC:3.5.1.98]
106978633  histone deacetylase 11 [KO:K11418] [EC:3.5.1.98]
106987851  cathepsin G [KO:K01319] [EC:3.4.21.20]
106979177  cathelicidin antimicrobial peptide [KO:K13916]
106975282  H(+)/Cl(-) exchange transporter 5 isoform X1 [KO:K05012]
106976519  H(+)/Cl(-) exchange transporter 3 isoform X1 [KO:K05012]
106971042  H(+)/Cl(-) exchange transporter 4 [KO:K05012]
106973788  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
  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
aju04010  MAPK signaling pathway
aju04020  Calcium signaling pathway
aju04140  Autophagy - animal
aju04151  PI3K-Akt signaling pathway
aju04610  Complement and coagulation cascades
aju04611  Platelet activation
aju04620  Toll-like receptor signaling pathway
aju04621  NOD-like receptor signaling pathway
aju04666  Fc gamma R-mediated phagocytosis
KO pathway
ko04613   
LinkDB

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