KEGG   PATHWAY: umr04613
Entry
umr04613                    Pathway                                
Name
Neutrophil extracellular trap formation - Ursus maritimus (polar bear)
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
umr04613  Neutrophil extracellular trap formation
umr04613

Organism
Ursus maritimus (polar bear) [GN:umr]
Gene
103656237  VWF; von Willebrand factor isoform X1 [KO:K03900]
103656671  GSDMD; gasdermin-D isoform X2 [KO:K20917]
103656991  SLC25A31; ADP/ATP translocase 4 [KO:K05863]
103657079  C5AR1; C5a anaphylatoxin chemotactic receptor 1 [KO:K04010]
103657310  FPR2; N-formyl peptide receptor 2 [KO:K04173]
103657827  MAPK3; mitogen-activated protein kinase 3 isoform X1 [KO:K04371] [EC:2.7.11.24]
103657863  ITGAL; integrin alpha-L isoform X1 [KO:K05718]
103657890  ITGAM; integrin alpha-M isoform X1 [KO:K06461]
103658031  [KO:K10159]
103658034  FGB; fibrinogen beta chain [KO:K03904]
103658035  FGA; fibrinogen alpha chain [KO:K03903]
103658036  FGG; fibrinogen gamma chain [KO:K03905]
103658150  CLCN3; H(+)/Cl(-) exchange transporter 3 isoform X4 [KO:K05012]
103658250  [KO:K06463]
103658850  HDAC9; histone deacetylase 9 isoform X1 [KO:K11409] [EC:3.5.1.98]
103659278  [KO:K11251]
103659563  HAT1; histone acetyltransferase type B catalytic subunit [KO:K11303] [EC:2.3.1.48]
103660092  MAP3K7; mitogen-activated protein kinase kinase kinase 7 isoform X1 [KO:K04427] [EC:2.7.11.25]
103660444  GP1BA; platelet glycoprotein Ib alpha chain [KO:K06261]
103660949  [KO:K11252]
103661038  AKT2; RAC-beta serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
103662093  PLCG2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2 isoform X1 [KO:K05859] [EC:3.1.4.11]
103662442  [KO:K04394] [EC:3.4.22.57 3.4.22.64]
103662443  CLCN5; H(+)/Cl(-) exchange transporter 5 [KO:K05012]
103662823  HDAC4; histone deacetylase 4 [KO:K11406] [EC:3.5.1.98]
103663192  SYK; tyrosine-protein kinase SYK isoform X1 [KO:K05855] [EC:2.7.10.2]
103663617  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X3 [KO:K02649]
103663723  HDAC3; histone deacetylase 3 isoform X1 [KO:K11404] [EC:3.5.1.98]
103663804  [KO:K11251]
103663818  VDAC1; voltage-dependent anion-selective channel protein 1 [KO:K05862]
103663868  [KO:K11252]
103664333  HMGB1; high mobility group protein B1 [KO:K10802]
103665033  [KO:K11252]
103665034  [KO:K11252]
103665040  [KO:K11251]
103665041  [KO:K11252]
103665042  [KO:K11251]
103665043  [KO:K11253]
103665044  [KO:K11254]
103665047  [KO:K11252]
103665050  [KO:K11254]
103665051  [KO:K11251]
103665052  [KO:K11252]
103665053  [KO:K11252]
103665054  [KO:K11254]
103665055  [KO:K11252]
103665056  [KO:K11251]
103665058  [KO:K11251]
103665059  [KO:K11252]
103665060  [KO:K11253]
103665061  [KO:K11251]
103665063  [KO:K11253]
103665064  [KO:K11251]
103665065  [KO:K11252]
103665066  [KO:K11252]
103665068  [KO:K11251]
103665070  [KO:K11252]
103665071  [KO:K11251]
103665072  [KO:K11252]
103665080  [KO:K11251]
103665081  [KO:K11252]
103665083  [KO:K11254]
103665085  [KO:K11251]
103665086  [KO:K11252]
103665098  [KO:K11252]
103665099  [KO:K11251]
103665100  [KO:K11252]
103665101  [KO:K11253]
103665102  [KO:K11251]
103665103  [KO:K11252]
103665181  [KO:K11251]
103665182  [KO:K11251]
103665188  [KO:K11253]
103665194  [KO:K11252]
103665196  [KO:K11253]
103665202  [KO:K11253]
103665204  [KO:K11253]
103665205  [KO:K11251]
103665451  MAPK14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
103665538  MAPK13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
103665592  ITGA2B; integrin alpha-IIb [KO:K06476]
103665747  [KO:K11253]
103665813  ACTG1; actin, cytoplasmic 2 [KO:K05692]
103665860  HDAC5; histone deacetylase 5 isoform X1 [KO:K11406] [EC:3.5.1.98]
103665892  ITGB3; integrin beta-3 [KO:K06493]
103665907  PRKCA; protein kinase C alpha type isoform X1 [KO:K02677] [EC:2.7.11.13]
103666331  SLC25A6; ADP/ATP translocase 3 [KO:K05863]
103666443  HDAC1; histone deacetylase 1 [KO:K06067] [EC:3.5.1.98]
103666611  PADI4; protein-arginine deiminase type-4 isoform X1 [KO:K24669]
103666660  MTOR; serine/threonine-protein kinase mTOR [KO:K07203] [EC:2.7.11.1]
103666688  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
103666874  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:2.7.1.153]
103667153  [KO:K11253]
103667463  MPO; myeloperoxidase [KO:K10789] [EC:1.11.2.2]
103667569  [KO:K11251]
103667570  [KO:K11251]
103667571  [KO:K11253]
103667572  [KO:K11252]
103667575  [KO:K11252]
103667576  [KO:K11251]
103667577  FCGR1A; high affinity immunoglobulin gamma Fc receptor I [KO:K06498]
103667578  [KO:K11252]
103667579  [KO:K11254]
103667606  [KO:K11253]
103667691  [KO:K06496]
103667846  VDAC2; voltage-dependent anion-selective channel protein 2 [KO:K15040]
103668010  [KO:K11251]
103668033  PPIF; peptidyl-prolyl cis-trans isomerase F, mitochondrial isoform X1 [KO:K09565] [EC:5.2.1.8]
103668101  TLR7; toll-like receptor 7 isoform X3 [KO:K05404]
103668102  TLR8; toll-like receptor 8 [KO:K10170]
103668135  CLCN4; LOW QUALITY PROTEIN: H(+)/Cl(-) exchange transporter 4 [KO:K05012]
103668228  [KO:K21421] [EC:1.-.-.-]
103668837  HDAC6; LOW QUALITY PROTEIN: histone deacetylase 6 [KO:K11407] [EC:3.5.1.98]
103668895  PRKCB; LOW QUALITY PROTEIN: protein kinase C beta type [KO:K19662] [EC:2.7.11.13]
103669135  CLEC7A; C-type lectin domain family 7 member A isoform X1 [KO:K10074]
103669286  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
103669506  HDAC11; histone deacetylase 11 [KO:K11418] [EC:3.5.1.98]
103669540  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
103669551  ATG7; ubiquitin-like modifier-activating enzyme ATG7 isoform X1 [KO:K08337]
103669754  PLCG1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 isoform X1 [KO:K01116] [EC:3.1.4.11]
103669776  SRC; proto-oncogene tyrosine-protein kinase Src [KO:K05704] [EC:2.7.10.2]
103670086  ACTB; actin, cytoplasmic 1 [KO:K05692]
103670095  RAC1; ras-related C3 botulinum toxin substrate 1 [KO:K04392]
103670166  NCF1; neutrophil cytosol factor 1 isoform X1 [KO:K08011]
103670372  C5; complement C5 [KO:K03994]
103670382  TLR4; toll-like receptor 4 [KO:K10160]
103670766  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
103672508  NCF2; neutrophil cytosol factor 2 [KO:K08010]
103672539  [KO:K04011]
103672914  PRKCG; protein kinase C gamma type [KO:K19663] [EC:2.7.11.13]
103673552  [KO:K05858] [EC:3.1.4.11]
103673846  [KO:K08009]
103674004  MAPK11; mitogen-activated protein kinase 11 [KO:K04441] [EC:2.7.11.24]
103674006  HDAC10; polyamine deacetylase HDAC10 isoform X1 [KO:K18671] [EC:3.5.1.98]
103674115  MAPK12; mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24]
103674425  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 isoform X1 [KO:K05858] [EC:3.1.4.11]
103674426  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 [KO:K05858] [EC:3.1.4.11]
103674566  [KO:K11251]
103674860  [KO:K13916]
103675162  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
103675458  [KO:K11252]
103675597  HDAC7; histone deacetylase 7 isoform X1 [KO:K11408] [EC:3.5.1.98]
103676125  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
103676407  RAC2; ras-related C3 botulinum toxin substrate 2 isoform X1 [KO:K07860]
103676418  NCF4; neutrophil cytosol factor 4 [KO:K08012]
103676791  AQP9; aquaporin-9 isoform X1 [KO:K09877]
103676878  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
103676974  HDAC2; histone deacetylase 2 [KO:K06067] [EC:3.5.1.98]
103677056  VDAC3; voltage-dependent anion-selective channel protein 3 [KO:K15041]
103677737  SLC25A5; ADP/ATP translocase 2 [KO:K05863]
103677773  [KO:K11254]
103677774  [KO:K11251]
103677932  [KO:K11251]
103677947  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
103678305  SELPLG; P-selectin glycoprotein ligand 1 [KO:K06544]
103678592  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
103678852  [KO:K11252]
103678853  [KO:K11252]
103678854  [KO:K11251]
103678855  [KO:K11253]
103679064  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
103679302  CTSG; cathepsin G [KO:K01319] [EC:3.4.21.20]
103679549  PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 [KO:K05858] [EC:3.1.4.11]
103679584  RELA; transcription factor p65 [KO:K04735]
103680190  HDAC8; histone deacetylase 8 isoform X1 [KO:K11405] [EC:3.5.1.98]
103680739  ITGB2; integrin beta-2 [KO:K06464]
103681007  SLC25A4; ADP/ATP translocase 1 [KO:K05863]
103681765  [KO:K01327] [EC:3.4.21.37]
103681834  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
103681871  C3; complement C3 [KO:K03990]
103682263  [KO:K11254]
103682274  AGER; advanced glycosylation end product-specific receptor [KO:K19722]
121099746  [KO:K05858] [EC:3.1.4.11]
121102015  [KO:K11252]
121102419  [KO:K11252]
121102451  [KO:K11252]
121102568  [KO:K11252]
121102918  [KO:K11251]
121103027  [KO:K11251]
121103760  [KO:K11251]
121106098  [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
  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
umr04010  MAPK signaling pathway
umr04020  Calcium signaling pathway
umr04140  Autophagy - animal
umr04151  PI3K-Akt signaling pathway
umr04610  Complement and coagulation cascades
umr04611  Platelet activation
umr04620  Toll-like receptor signaling pathway
umr04621  NOD-like receptor signaling pathway
umr04666  Fc gamma R-mediated phagocytosis
KO pathway
ko04613   

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