KEGG   PATHWAY: pleu04613
Entry
pleu04613                   Pathway                                
Name
Neutrophil extracellular trap formation - Peromyscus leucopus (white-footed mouse)
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
pleu04613  Neutrophil extracellular trap formation
pleu04613

Organism
Peromyscus leucopus (white-footed mouse) [GN:pleu]
Gene
114680598  Actg1; LOW QUALITY PROTEIN: actin, cytoplasmic 2 [KO:K05692]
114680674  Plcb3; LOW QUALITY PROTEIN: 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 [KO:K05858] [EC:3.1.4.11]
114681283  Hdac11; histone deacetylase 11 isoform X1 [KO:K11418] [EC:3.5.1.98]
114681439  C5ar1; C5a anaphylatoxin chemotactic receptor 1 [KO:K04010]
114681524  Akt2; RAC-beta serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
114681835  Src; proto-oncogene tyrosine-protein kinase Src isoform X1 [KO:K05704] [EC:2.7.10.2]
114681917  Vdac1; voltage-dependent anion-selective channel protein 1 [KO:K05862]
114681967  [KO:K11252]
114682099  Rela; transcription factor p65 [KO:K04735]
114682366  [KO:K11253]
114682367  [KO:K06498]
114682387  [KO:K11254]
114682388  [KO:K11251]
114682389  [KO:K11251]
114682390  [KO:K11252]
114682398  [KO:K11252]
114682405  [KO:K11251]
114682406  [KO:K11251]
114682732  Mapk1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
114682941  Fga; fibrinogen alpha chain [KO:K03903]
114682942  Fgb; fibrinogen beta chain [KO:K03904]
114682943  Fgg; fibrinogen gamma chain [KO:K03905]
114682988  [KO:K11252]
114682996  [KO:K11253]
114683000  [KO:K11251]
114683001  [KO:K11252]
114683008  [KO:K11253]
114683075  [KO:K06067] [EC:3.5.1.98]
114683205  Nfkb1; nuclear factor NF-kappa-B p105 subunit [KO:K02580]
114683296  [KO:K11251]
114683403  [KO:K11253]
114683788  [KO:K11253]
114684032  Pik3cd; LOW QUALITY PROTEIN: phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:2.7.1.153]
114684136  Elane; neutrophil elastase [KO:K01327] [EC:3.4.21.37]
114684256  [KO:K05692]
114685191  Fpr1; fMet-Leu-Phe receptor [KO:K04172]
114685192  Fpr2; N-formyl peptide receptor 2 [KO:K04173]
114686198  Selplg; LOW QUALITY PROTEIN: P-selectin glycoprotein ligand 1 [KO:K06544]
114686242  [KO:K11251]
114686332  [KO:K06261]
114686338  [KO:K06261]
114686345  [KO:K06261]
114686534  C3; complement C3 isoform X1 [KO:K03990]
114686853  Casp1; caspase-1 [KO:K01370] [EC:3.4.22.36]
114687196  [KO:K11251]
114687203  [KO:K11251]
114687204  [KO:K11251]
114687523  Prkcg; protein kinase C gamma type [KO:K19663] [EC:2.7.11.13]
114687532  [KO:K04011]
114687533  Cr1l; complement component receptor 1-like protein isoform X1 [KO:K04011]
114687855  [KO:K11251]
114688121  Map2k2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
114688930  [KO:K11251]
114688966  Pik3r2; phosphatidylinositol 3-kinase regulatory subunit beta isoform X1 [KO:K02649]
114689009  [KO:K11251]
114689480  Syk; tyrosine-protein kinase SYK isoform X1 [KO:K05855] [EC:2.7.10.2]
114689627  Atg7; ubiquitin-like modifier-activating enzyme ATG7 [KO:K08337]
114689636  Raf1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
114689891  [KO:K06463]
114690001  [KO:K06496]
114690439  Prkca; protein kinase C alpha type [KO:K02677] [EC:2.7.11.13]
114690628  [KO:K11253]
114690660  Akt3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
114690738  Aqp9; aquaporin-9 isoform X1 [KO:K09877]
114691171  [KO:K11251]
114691497  Map2k1; dual specificity mitogen-activated protein kinase kinase 1 isoform X2 [KO:K04368] [EC:2.7.12.2]
114691719  [KO:K10802]
114691928  [KO:K05862]
114692073  [KO:K11253]
114692203  Prkcb; protein kinase C beta type isoform X1 [KO:K19662] [EC:2.7.11.13]
114692579  Plcg1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 [KO:K01116] [EC:3.1.4.11]
114693016  Hdac10; polyamine deacetylase HDAC10 isoform X1 [KO:K18671] [EC:3.5.1.98]
114693019  Mapk12; mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24]
114693020  Mapk11; mitogen-activated protein kinase 11 isoform X5 [KO:K04441] [EC:2.7.11.24]
114693559  Pik3cb; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
114693708  Ncf1; neutrophil cytosol factor 1 [KO:K08011]
114693970  [KO:K11251]
114694150  [KO:K20917]
114694222  Ncf4; neutrophil cytosol factor 4 [KO:K08012]
114694231  Rac2; ras-related C3 botulinum toxin substrate 2 [KO:K07860]
114694445  [KO:K05863]
114694702  [KO:K11252]
114694704  [KO:K11252]
114694848  [KO:K10802]
114695027  [KO:K11251]
114695055  [KO:K11254]
114695335  Pik3ca; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
114695419  Map3k7; mitogen-activated protein kinase kinase kinase 7 isoform X1 [KO:K04427] [EC:2.7.11.25]
114696006  [KO:K11253]
114696529  Itgb2; integrin beta-2 [KO:K06464]
114696875  Hdac2; histone deacetylase 2 [KO:K06067] [EC:3.5.1.98]
114697163  [KO:K11253]
114697457  Plcg2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2 [KO:K05859] [EC:3.1.4.11]
114697698  [KO:K11253]
114697740  [KO:K11253]
114699146  Hmgb1; high mobility group protein B1 [KO:K10802]
114699237  [KO:K10789] [EC:1.11.2.2]
114699257  [KO:K10789] [EC:1.11.2.2]
114699396  Hdac9; histone deacetylase 9 isoform X1 [KO:K11409] [EC:3.5.1.98]
114699709  [KO:K11253]
114700064  [KO:K11251]
114700069  [KO:K11252]
114700072  [KO:K11252]
114700081  [KO:K11253]
114700094  [KO:K11252]
114700101  [KO:K11251]
114700106  [KO:K11251]
114700112  [KO:K11251]
114700121  [KO:K11251]
114700131  [KO:K11252]
114700141  [KO:K11252]
114700156  [KO:K11252]
114700172  [KO:K11254]
114700184  [KO:K11253]
114700220  Vdac2; voltage-dependent anion-selective channel protein 2 [KO:K15040]
114700344  [KO:K06464]
114700479  [KO:K11253]
114700487  [KO:K11253]
114700495  [KO:K11253]
114700526  [KO:K11251]
114700545  [KO:K11251]
114700551  [KO:K11251]
114700556  [KO:K11251]
114700562  [KO:K11251]
114700573  [KO:K11251]
114700585  [KO:K11252]
114700598  [KO:K11252]
114700607  [KO:K11252]
114700614  [KO:K11252]
114700621  [KO:K11252]
114700630  [KO:K11252]
114700637  [KO:K11252]
114700647  [KO:K11252]
114700659  [KO:K11252]
114700669  [KO:K11252]
114700679  [KO:K11254]
114700689  [KO:K11254]
114700697  [KO:K11254]
114700703  [KO:K11254]
114700707  Hdac4; histone deacetylase 4 [KO:K11406] [EC:3.5.1.98]
114700745  [KO:K11253]
114700848  Padi4; LOW QUALITY PROTEIN: protein-arginine deiminase type-4 [KO:K24669]
114700968  [KO:K08009]
114701102  Clcn3; H(+)/Cl(-) exchange transporter 3 isoform X1 [KO:K05012]
114701179  Slc25a4; ADP/ATP translocase 1 [KO:K05863]
114701279  Clcn5; H(+)/Cl(-) exchange transporter 5 isoform X1 [KO:K05012]
114701304  Hdac6; histone deacetylase 6 isoform X1 [KO:K11407] [EC:3.5.1.98]
114701319  [KO:K21421] [EC:1.-.-.-]
114701323  [KO:K11251]
114701415  Clec7a; C-type lectin domain family 7 member A isoform X2 [KO:K10074]
114701680  [KO:K11252]
114701690  [KO:K11251]
114702022  [KO:K11253]
114702220  Hdac5; histone deacetylase 5 isoform X1 [KO:K11406] [EC:3.5.1.98]
114702233  Itga2b; LOW QUALITY PROTEIN: integrin alpha-IIb [KO:K06476]
114702284  Itgb3; integrin beta-3 [KO:K06493]
114702483  [KO:K10802]
114702940  Tlr7; toll-like receptor 7 [KO:K05404]
114702951  Tlr8; toll-like receptor 8 [KO:K10170]
114703046  Akt1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
114703666  Plcb4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X2 [KO:K05858] [EC:3.1.4.11]
114703672  Plcb1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 isoform X1 [KO:K05858] [EC:3.1.4.11]
114703850  Pik3r1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
114704093  [KO:K11251]
114704332  Mapk3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
114704367  Itgal; integrin alpha-L isoform X1 [KO:K05718]
114704404  [KO:K06461]
114704483  Hat1; histone acetyltransferase type B catalytic subunit isoform X1 [KO:K11303] [EC:2.3.1.48]
114704610  Clcn4; H(+)/Cl(-) exchange transporter 4 isoform X1 [KO:K05012]
114704700  C5; complement C5 [KO:K03994]
114704754  [KO:K11251]
114705253  [KO:K13916]
114705416  Slc25a5; ADP/ATP translocase 2 [KO:K05863]
114705499  Actb; actin, cytoplasmic 1 [KO:K05692]
114705645  Hdac1; histone deacetylase 1 [KO:K06067] [EC:3.5.1.98]
114705743  Vdac3; voltage-dependent anion-selective channel protein 3 isoform X1 [KO:K15041]
114705782  Tlr4; toll-like receptor 4 isoform X2 [KO:K10160]
114705813  Ager; advanced glycosylation end product-specific receptor isoform X1 [KO:K19722]
114705921  Plcb2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 [KO:K05858] [EC:3.1.4.11]
114706162  Mapk13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
114706165  Mapk14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
114706250  [KO:K11251]
114706924  Pik3r3; phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649]
114707068  [KO:K11253]
114707535  Rac1; ras-related C3 botulinum toxin substrate 1 isoform X1 [KO:K04392]
114708323  [KO:K11253]
114708513  Hdac7; histone deacetylase 7 isoform X2 [KO:K11408] [EC:3.5.1.98]
114708647  Hdac8; histone deacetylase 8 [KO:K11405] [EC:3.5.1.98]
114708764  [KO:K01319] [EC:3.4.21.20]
114708777  Vwf; LOW QUALITY PROTEIN: von Willebrand factor [KO:K03900]
114709010  [KO:K11251]
114709626  Ppif; peptidyl-prolyl cis-trans isomerase F, mitochondrial isoform X1 [KO:K09565] [EC:5.2.1.8]
114709670  Mtor; LOW QUALITY PROTEIN: serine/threonine-protein kinase mTOR [KO:K07203] [EC:2.7.11.1]
114710188  Tlr2; toll-like receptor 2 [KO:K10159]
114710523  [KO:K04371] [EC:2.7.11.24]
114710781  Slc25a31; ADP/ATP translocase 4 [KO:K05863]
114711016  [KO:K05863]
119086086  [KO:K11251]
119086087  Fcgr2a; low affinity immunoglobulin gamma Fc region receptor II-a isoform X1 [KO:K06472]
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 9:369 (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 9:365 (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
pleu04010  MAPK signaling pathway
pleu04020  Calcium signaling pathway
pleu04140  Autophagy - animal
pleu04151  PI3K-Akt signaling pathway
pleu04610  Complement and coagulation cascades
pleu04611  Platelet activation
pleu04620  Toll-like receptor signaling pathway
pleu04621  NOD-like receptor signaling pathway
pleu04666  Fc gamma R-mediated phagosome formation
KO pathway
ko04613   

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