KEGG   PATHWAY: dle04613
Entry
dle04613                    Pathway                                
Name
Neutrophil extracellular trap formation - Delphinapterus leucas (beluga whale)
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
dle04613  Neutrophil extracellular trap formation
dle04613

Organism
Delphinapterus leucas (beluga whale) [GN:dle]
Gene
111162742  SELPLG; P-selectin glycoprotein ligand 1 [KO:K06544]
111162931  [KO:K11253]
111163022  MAPK1; mitogen-activated protein kinase 1 isoform X1 [KO:K04371] [EC:2.7.11.24]
111163266  [KO:K24669]
111163673  MPO; myeloperoxidase [KO:K10789] [EC:1.11.2.2]
111163761  MAP3K7; mitogen-activated protein kinase kinase kinase 7 isoform X1 [KO:K04427] [EC:2.7.11.25]
111164170  [KO:K11253]
111164824  [KO:K06067] [EC:3.5.1.98]
111164829  [KO:K06067] [EC:3.5.1.98]
111165112  GSDMD; gasdermin-D isoform X1 [KO:K20917]
111165617  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X1 [KO:K05858] [EC:3.1.4.11]
111165653  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 isoform X1 [KO:K05858] [EC:3.1.4.11]
111165889  SLC25A31; ADP/ATP translocase 4 [KO:K05863]
111165994  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 isoform X1 [KO:K04369] [EC:2.7.12.2]
111166019  C3; complement C3 isoform X1 [KO:K03990]
111166652  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
111167209  CLCN4; H(+)/Cl(-) exchange transporter 4 [KO:K05012]
111167211  TLR7; toll-like receptor 7 isoform X1 [KO:K05404]
111167212  TLR8; toll-like receptor 8 [KO:K10170]
111167319  SELP; P-selectin isoform X1 [KO:K06496]
111167415  [KO:K11251]
111167555  [KO:K04394] [EC:3.4.22.57 3.4.22.64]
111167579  CASP1; caspase-1 [KO:K01370] [EC:3.4.22.36]
111167662  SYK; tyrosine-protein kinase SYK isoform X1 [KO:K05855] [EC:2.7.10.2]
111167944  [KO:K11253]
111168263  SLC25A6; ADP/ATP translocase 3 [KO:K05863]
111168441  [KO:K11253]
111168442  [KO:K11251]
111168443  [KO:K11251]
111168444  [KO:K11251]
111168445  [KO:K11252]
111168446  [KO:K11252]
111168448  [KO:K11252]
111168449  [KO:K11252]
111168460  [KO:K11252]
111168481  [KO:K11253]
111168485  [KO:K11253]
111168512  [KO:K11251]
111168514  [KO:K11251]
111168515  [KO:K11253]
111168516  [KO:K11253]
111168517  [KO:K11251]
111168518  [KO:K11252]
111168519  [KO:K11251]
111168520  [KO:K11251]
111168521  [KO:K11251]
111168523  [KO:K11252]
111168524  [KO:K11252]
111168525  [KO:K11252]
111168526  [KO:K11252]
111168527  [KO:K11252]
111168528  [KO:K11252]
111168529  [KO:K11252]
111168530  [KO:K11252]
111168535  [KO:K11254]
111168539  [KO:K11253]
111168543  [KO:K11253]
111168544  [KO:K11252]
111168549  [KO:K11252]
111168550  [KO:K11251]
111168809  HDAC11; histone deacetylase 11 isoform X2 [KO:K11418] [EC:3.5.1.98]
111168973  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
111168983  ATG7; ubiquitin-like modifier-activating enzyme ATG7 isoform X1 [KO:K08337]
111169059  SLC25A5; ADP/ATP translocase 2 [KO:K05863]
111169299  [KO:K11253]
111169314  [KO:K11251]
111169315  [KO:K11252]
111169480  CLCN5; H(+)/Cl(-) exchange transporter 5 isoform X1 [KO:K05012]
111169522  HDAC6; histone deacetylase 6 isoform X1 [KO:K11407] [EC:3.5.1.98]
111169704  [KO:K11253]
111169736  [KO:K11252]
111169737  [KO:K11253]
111169747  [KO:K11251]
111169748  [KO:K11251]
111169749  [KO:K11252]
111170186  HDAC5; histone deacetylase 5 isoform X2 [KO:K11406] [EC:3.5.1.98]
111170236  ITGA2B; integrin alpha-IIb [KO:K06476]
111170344  ACTB; actin, cytoplasmic 1 [KO:K05692]
111170413  [KO:K06463]
111170444  HDAC8; histone deacetylase 8 isoform X1 [KO:K11405] [EC:3.5.1.98]
111170450  [KO:K21421] [EC:1.-.-.-]
111170497  ELANE; neutrophil elastase [KO:K01327] [EC:3.4.21.37]
111170515  AZU1; azurocidin [KO:K24665]
111170741  [KO:K11251]
111170949  AGER; advanced glycosylation end product-specific receptor isoform X1 [KO:K19722]
111171039  [KO:K13916]
111171040  [KO:K13916]
111171041  [KO:K13916]
111171097  [KO:K01319] [EC:3.4.21.20]
111171120  [KO:K11252]
111171154  [KO:K11251]
111171155  [KO:K11252]
111171291  [KO:K11253]
111171987  HDAC4; histone deacetylase 4 isoform X1 [KO:K11406] [EC:3.5.1.98]
111172865  HAT1; histone acetyltransferase type B catalytic subunit [KO:K11303] [EC:2.3.1.48]
111173318  [KO:K11253]
111173410  SLC25A4; ADP/ATP translocase 1 [KO:K05863]
111173555  VDAC3; voltage-dependent anion-selective channel protein 3 [KO:K15041]
111173839  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
111174072  HDAC7; histone deacetylase 7 isoform X2 [KO:K11408] [EC:3.5.1.98]
111174439  CAMP; cathelicidin antimicrobial peptide isoform X1 [KO:K13916]
111175202  HMGB1; high mobility group protein B1 [KO:K10802]
111175514  HDAC1; histone deacetylase 1 isoform X1 [KO:K06067] [EC:3.5.1.98]
111175760  [KO:K02649]
111176008  AKT1; RAC-alpha serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
111176651  VWF; von Willebrand factor [KO:K03900]
111176743  [KO:K11252]
111176754  [KO:K10074]
111176794  [KO:K11251]
111177265  C5; complement C5 isoform X1 [KO:K03994]
111177277  TLR4; toll-like receptor 4 isoform X1 [KO:K10160]
111177525  [KO:K11253]
111177559  AKT3; RAC-gamma serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
111177661  AQP9; aquaporin-9 [KO:K09877]
111177745  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
111178736  MAPK14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
111178738  MAPK13; mitogen-activated protein kinase 13 isoform X2 [KO:K04441] [EC:2.7.11.24]
111179105  [KO:K11251]
111179110  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
111179235  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
111179403  [KO:K08009]
111179463  PLCG2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2 [KO:K05859] [EC:3.1.4.11]
111180688  C5AR1; C5a anaphylatoxin chemotactic receptor 1 isoform X1 [KO:K04010]
111180855  AKT2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
111180981  PRKCG; protein kinase C gamma type isoform X1 [KO:K19663] [EC:2.7.11.13]
111181753  PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 isoform X1 [KO:K05858] [EC:3.1.4.11]
111181827  HDAC9; histone deacetylase 9 isoform X1 [KO:K11409] [EC:3.5.1.98]
111181886  RAC1; ras-related C3 botulinum toxin substrate 1 [KO:K04392]
111182060  NCF1; neutrophil cytosol factor 1 isoform X1 [KO:K08011]
111182142  ITGAL; integrin alpha-L [KO:K05718]
111182181  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
111182232  PRKCB; protein kinase C beta type isoform X1 [KO:K19662] [EC:2.7.11.13]
111182295  [KO:K06461]
111182441  VDAC1; voltage-dependent anion-selective channel protein 1 [KO:K05862]
111182462  [KO:K11251]
111182589  ITGB3; integrin beta-3 isoform X1 [KO:K06493]
111182710  ACTG1; actin, cytoplasmic 2 [KO:K05692]
111182816  [KO:K11253]
111182917  PRKCA; protein kinase C alpha type isoform X1 [KO:K02677] [EC:2.7.11.13]
111183021  HDAC3; histone deacetylase 3 [KO:K11404] [EC:3.5.1.98]
111183465  [KO:K11251]
111183542  VDAC2; voltage-dependent anion-selective channel protein 2 [KO:K15040]
111183554  PPIF; peptidyl-prolyl cis-trans isomerase F, mitochondrial [KO:K09565] [EC:5.2.1.8]
111183745  RELA; transcription factor p65 isoform X1 [KO:K04735]
111183812  PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 [KO:K05858] [EC:3.1.4.11]
111184170  PLCG1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 isoform X1 [KO:K01116] [EC:3.1.4.11]
111184199  SRC; proto-oncogene tyrosine-protein kinase Src isoform X1 [KO:K05704] [EC:2.7.10.2]
111184525  [KO:K11251]
111184640  NCF2; neutrophil cytosol factor 2 isoform X1 [KO:K08010]
111184732  CR1; complement receptor type 1 isoform X1 [KO:K04011]
111185343  CLCN3; H(+)/Cl(-) exchange transporter 3 isoform X1 [KO:K05012]
111185947  GP1BA; platelet glycoprotein Ib alpha chain [KO:K06261]
111185984  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
111186216  RAC2; ras-related C3 botulinum toxin substrate 2 isoform X1 [KO:K07860]
111186360  HDAC10; polyamine deacetylase HDAC10 isoform X1 [KO:K18671] [EC:3.5.1.98]
111186361  MAPK12; mitogen-activated protein kinase 12 isoform X1 [KO:K04441] [EC:2.7.11.24]
111186364  MAPK11; mitogen-activated protein kinase 11 isoform X1 [KO:K04441] [EC:2.7.11.24]
111186386  [KO:K08012]
111186435  ITGB2; integrin beta-2 [KO:K06464]
111187262  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:2.7.1.153]
111187265  MTOR; serine/threonine-protein kinase mTOR isoform X1 [KO:K07203] [EC:2.7.11.1]
111187714  TLR2; toll-like receptor 2 [KO:K10159]
111187742  FGG; fibrinogen gamma chain isoform X1 [KO:K03905]
111187747  FGB; fibrinogen beta chain isoform X1 [KO:K03904]
111187748  FGA; fibrinogen alpha chain [KO:K03903]
111187847  [KO:K08012]
111187864  [KO:K15041]
115802015  [KO:K11253]
115802482  [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
dle04010  MAPK signaling pathway
dle04020  Calcium signaling pathway
dle04140  Autophagy - animal
dle04151  PI3K-Akt signaling pathway
dle04610  Complement and coagulation cascades
dle04611  Platelet activation
dle04620  Toll-like receptor signaling pathway
dle04621  NOD-like receptor signaling pathway
dle04666  Fc gamma R-mediated phagocytosis
KO pathway
ko04613   

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