KEGG   PATHWAY: panu04613
Entry
panu04613                   Pathway                                
Name
Neutrophil extracellular trap formation - Papio anubis (olive baboon)
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
panu04613  Neutrophil extracellular trap formation
panu04613

Organism
Papio anubis (olive baboon) [GN:panu]
Gene
100126738  FCGR3A; low affinity immunoglobulin gamma Fc region receptor III precursor [KO:K06463]
100137333  PRKCG; protein kinase C gamma type [KO:K19663] [EC:2.7.11.13]
100137373  HMGB1; high mobility group protein B1 [KO:K10802]
100137383  HIST1H3A; histone H3.1 [KO:K11253]
100381179  AKT2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
100510873  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X4 [KO:K02649]
100997257  PPIF; peptidyl-prolyl cis-trans isomerase F, mitochondrial [KO:K09565] [EC:5.2.1.8]
100997319  ACTG1; actin, cytoplasmic 2 [KO:K05692]
100997634  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
100998272  [KO:K11253]
100998763  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 isoform X1 [KO:K05858] [EC:3.1.4.11]
100998956  SLC25A4; ADP/ATP translocase 1 [KO:K05863]
100998964  [KO:K11251]
100999120  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X5 [KO:K05858] [EC:3.1.4.11]
101000269  [KO:K11253]
101000402  AKT1; RAC-alpha serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
101000536  HDAC10; polyamine deacetylase HDAC10 isoform X8 [KO:K18671] [EC:3.5.1.98]
101000631  SLC25A5; ADP/ATP translocase 2 [KO:K05863]
101001103  MAPK12; mitogen-activated protein kinase 12 isoform X2 [KO:K04441] [EC:2.7.11.24]
101001711  [KO:K11251]
101002132  [KO:K11253]
101002278  PIK3CD; LOW QUALITY PROTEIN: phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:2.7.1.153]
101002393  MAPK11; mitogen-activated protein kinase 11 [KO:K04441] [EC:2.7.11.24]
101002971  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649]
101003204  [KO:K11252]
101003234  [KO:K11251]
101003247  HDAC5; histone deacetylase 5 isoform X1 [KO:K11406] [EC:3.5.1.98]
101003340  C5; complement C5 isoform X1 [KO:K03994]
101003684  HDAC11; histone deacetylase 11 isoform X1 [KO:K11418] [EC:3.5.1.98]
101003762  [KO:K11251]
101003793  FCGR1A; high affinity immunoglobulin gamma Fc receptor I isoform X2 [KO:K06498]
101003935  RAC1; ras-related C3 botulinum toxin substrate 1 isoform X1 [KO:K04392]
101004074  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 isoform X1 [KO:K04369] [EC:2.7.12.2]
101004087  ITGAM; LOW QUALITY PROTEIN: integrin alpha-M [KO:K06461]
101004091  PLCG2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2 isoform X1 [KO:K05859] [EC:3.1.4.11]
101004137  PADI4; protein-arginine deiminase type-4 isoform X1 [KO:K24669]
101004146  [KO:K11251]
101004461  [KO:K06856]
101004536  [KO:K11253]
101004843  HDAC4; histone deacetylase 4 isoform X1 [KO:K11406] [EC:3.5.1.98]
101004976  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
101005674  [KO:K04394] [EC:3.4.22.57 3.4.22.64]
101005729  [KO:K08009]
101006236  [KO:K11252]
101006748  C3; complement C3 [KO:K03990]
101006756  MAPK3; mitogen-activated protein kinase 3 isoform X1 [KO:K04371] [EC:2.7.11.24]
101006760  [KO:K21421] [EC:1.-.-.-]
101006767  NCF4; neutrophil cytosol factor 4 isoform X2 [KO:K08012]
101006770  [KO:K11253]
101006831  CASP1; caspase-1 isoform X1 [KO:K01370] [EC:3.4.22.36]
101007374  NCF2; neutrophil cytosol factor 2 isoform X1 [KO:K08010]
101007521  [KO:K11253]
101008118  [KO:K11253]
101008394  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 isoform X1 [KO:K04368] [EC:2.7.12.2]
101008482  [KO:K11252]
101008696  [KO:K01370] [EC:3.4.22.36]
101008699  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
101008754  [KO:K11252]
101008777  [KO:K11253]
101008831  [KO:K11252]
101008890  SELPLG; P-selectin glycoprotein ligand 1 isoform X1 [KO:K06544]
101009024  SELP; P-selectin [KO:K06496]
101009029  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
101009041  TLR4; toll-like receptor 4 isoform X1 [KO:K10160]
101009125  CLEC7A; C-type lectin domain family 7 member A isoform X4 [KO:K10074]
101009309  HDAC6; histone deacetylase 6 isoform X1 [KO:K11407] [EC:3.5.1.98]
101009375  [KO:K01370] [EC:3.4.22.36]
101009395  ITGA2B; integrin alpha-IIb [KO:K06476]
101009552  VDAC2; voltage-dependent anion-selective channel protein 2 isoform X1 [KO:K15040]
101009578  [KO:K11252]
101009750  SLC25A31; ADP/ATP translocase 4 isoform X1 [KO:K05863]
101009865  PRKCB; protein kinase C beta type isoform X1 [KO:K19662] [EC:2.7.11.13]
101009919  [KO:K11251]
101009922  FCGR2A; low affinity immunoglobulin gamma Fc region receptor II-a isoform X1 [KO:K06472]
101009981  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
101010000  PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 isoform X4 [KO:K05858] [EC:3.1.4.11]
101010089  [KO:K11252]
101010160  HDAC1; histone deacetylase 1 isoform X1 [KO:K06067] [EC:3.5.1.98]
101010649  [KO:K11253]
101010784  [KO:K11253]
101010987  [KO:K11252]
101011060  [KO:K11251]
101011165  MPO; myeloperoxidase isoform X1 [KO:K10789] [EC:1.11.2.2]
101011394  [KO:K11252]
101011576  VWF; von Willebrand factor isoform X1 [KO:K03900]
101011806  GSDMD; gasdermin-D isoform X3 [KO:K20917]
101011982  [KO:K11254]
101012041  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
101012095  ITGB3; integrin beta-3 [KO:K06493]
101012165  PLCG1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 isoform X2 [KO:K01116] [EC:3.1.4.11]
101012251  SIGLEC9; sialic acid-binding Ig-like lectin 9 isoform X1 [KO:K06740]
101012342  [KO:K11251]
101012903  PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 [KO:K05858] [EC:3.1.4.11]
101013055  MAP3K7; mitogen-activated protein kinase kinase kinase 7 isoform X1 [KO:K04427] [EC:2.7.11.25]
101013677  [KO:K11253]
101013836  [KO:K11254]
101014612  [KO:K11254]
101014648  CLCN4; H(+)/Cl(-) exchange transporter 4 isoform X2 [KO:K05012]
101014797  [KO:K11251]
101014955  ITGB2; integrin beta-2 isoform X3 [KO:K06464]
101015041  MTOR; serine/threonine-protein kinase mTOR isoform X2 [KO:K07203] [EC:2.7.11.1]
101015332  [KO:K11251]
101015677  [KO:K11252]
101016129  [KO:K11253]
101016399  [KO:K11252]
101016465  RAC2; ras-related C3 botulinum toxin substrate 2 isoform X1 [KO:K07860]
101016492  [KO:K04011]
101016532  PRKCA; protein kinase C alpha type isoform X4 [KO:K02677] [EC:2.7.11.13]
101016765  [KO:K11253]
101017078  RELA; transcription factor p65 isoform X1 [KO:K04735]
101017082  CAMP; cathelicidin antimicrobial peptide isoform X1 [KO:K13916]
101017105  [KO:K11251]
101017243  FGB; fibrinogen beta chain [KO:K03904]
101017461  [KO:K11251]
101017602  FGA; LOW QUALITY PROTEIN: fibrinogen alpha chain [KO:K03903]
101017813  [KO:K11252]
101017958  FGG; fibrinogen gamma chain isoform X2 [KO:K03905]
101018174  [KO:K11253]
101018399  ATG7; ubiquitin-like modifier-activating enzyme ATG7 isoform X1 [KO:K08337]
101018547  [KO:K11251]
101018889  [KO:K11251]
101019427  VDAC3; voltage-dependent anion-selective channel protein 3 isoform X2 [KO:K15041]
101019598  [KO:K11251]
101019886  [KO:K11251]
101019919  [KO:K11252]
101020272  [KO:K11252]
101020343  TLR7; toll-like receptor 7 isoform X1 [KO:K05404]
101020537  [KO:K11252]
101020566  VDAC1; voltage-dependent anion-selective channel protein 1 [KO:K05862]
101020627  [KO:K11251]
101020657  NCF1; neutrophil cytosol factor 1 [KO:K08011]
101020664  [KO:K11253]
101020701  TLR8; toll-like receptor 8 isoform X1 [KO:K10170]
101020893  [KO:K11252]
101020977  [KO:K11253]
101021003  [KO:K11251]
101021227  [KO:K11251]
101021267  HDAC8; histone deacetylase 8 isoform X1 [KO:K11405] [EC:3.5.1.98]
101021342  [KO:K11252]
101021583  [KO:K11252]
101021610  FPR1; fMet-Leu-Phe receptor [KO:K04172]
101021735  [KO:K11251]
101021945  [KO:K11254]
101022109  [KO:K11253]
101022225  ITGAL; integrin alpha-L isoform X1 [KO:K05718]
101022294  [KO:K11252]
101022463  CLCN5; H(+)/Cl(-) exchange transporter 5 isoform X1 [KO:K05012]
101022644  [KO:K11251]
101022664  CLCN3; H(+)/Cl(-) exchange transporter 3 isoform X1 [KO:K05012]
101022666  FPR2; N-formyl peptide receptor 2 [KO:K04173]
101023703  [KO:K11252]
101023731  FPR3; N-formyl peptide receptor 3 [KO:K04173]
101024056  [KO:K11252]
101024178  HDAC9; histone deacetylase 9 isoform X26 [KO:K11409] [EC:3.5.1.98]
101024189  MAPK14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
101024314  C5AR1; C5a anaphylatoxin chemotactic receptor 1 isoform X2 [KO:K04010]
101024405  [KO:K11254]
101024528  GP1BA; LOW QUALITY PROTEIN: platelet glycoprotein Ib alpha chain [KO:K06261]
101024566  HDAC3; histone deacetylase 3 isoform X1 [KO:K11404] [EC:3.5.1.98]
101024771  MAPK13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
101024777  HDAC2; histone deacetylase 2 isoform X1 [KO:K06067] [EC:3.5.1.98]
101024880  SYK; tyrosine-protein kinase SYK isoform X6 [KO:K05855] [EC:2.7.10.2]
101024954  HDAC7; LOW QUALITY PROTEIN: histone deacetylase 7 [KO:K11408] [EC:3.5.1.98]
101024963  HAT1; histone acetyltransferase type B catalytic subunit isoform X1 [KO:K11303] [EC:2.3.1.48]
101025041  SLC25A6; ADP/ATP translocase 3 [KO:K05863]
101025530  SRC; proto-oncogene tyrosine-protein kinase Src isoform X1 [KO:K05704] [EC:2.7.10.2]
101026060  [KO:K11252]
101026781  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X6 [KO:K02580]
101026869  ACTB; actin, cytoplasmic 1 [KO:K05692]
103875593  [KO:K11254]
103875614  [KO:K11251]
103883343  [KO:K11252]
103883540  [KO:K11251]
103883547  [KO:K11251]
103884712  TLR2; toll-like receptor 2 [KO:K10159]
108580864  [KO:K11253]
108580865  [KO:K11253]
110740355  [KO:K11252]
110741987  [KO:K05692]
110742490  [KO:K11253]
116271018  [KO:K11254]
116275257  [KO:K11253]
116275258  [KO:K11253]
116275259  [KO:K11252]
116275409  [KO:K11253]
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
panu04010  MAPK signaling pathway
panu04020  Calcium signaling pathway
panu04140  Autophagy - animal
panu04151  PI3K-Akt signaling pathway
panu04610  Complement and coagulation cascades
panu04611  Platelet activation
panu04620  Toll-like receptor signaling pathway
panu04621  NOD-like receptor signaling pathway
panu04666  Fc gamma R-mediated phagocytosis
KO pathway
ko04613   

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