KEGG   PATHWAY: lruf04613
Entry
lruf04613                   Pathway                                
Name
Neutrophil extracellular trap formation - Lynx rufus (bobcat)
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
lruf04613  Neutrophil extracellular trap formation
lruf04613

Organism
Lynx rufus (bobcat) [GN:lruf]
Gene
124509902  low affinity immunoglobulin gamma Fc region receptor III-A-like [KO:K06463]
124527767  tyrosine-protein kinase SYK isoform X1 [KO:K05855] [EC:2.7.10.2]
124528290  mitogen-activated protein kinase kinase kinase 7 isoform X1 [KO:K04427] [EC:2.7.11.25]
124523760  RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
124508471  dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
124524782  dual specificity mitogen-activated protein kinase kinase 2 isoform X1 [KO:K04369] [EC:2.7.12.2]
124517731  mitogen-activated protein kinase 3 isoform X1 [KO:K04371] [EC:2.7.11.24]
124519861  mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
124509440  cytochrome b-245 heavy chain isoform X1 [KO:K21421] [EC:1.-.-.-]
124519160  neutrophil cytosol factor 1 isoform X1 [KO:K08011]
124511575  cytochrome b-245 light chain isoform X1 [KO:K08009]
124510150  neutrophil cytosol factor 2 [KO:K08010]
124501203  neutrophil cytosol factor 4 isoform X1 [KO:K08012]
124519305  ras-related C3 botulinum toxin substrate 1 [KO:K04392]
124501030  ras-related C3 botulinum toxin substrate 2 isoform X1 [KO:K07860]
124509347  toll-like receptor 7 [KO:K05404]
124509349  toll-like receptor 8 [KO:K10170]
124527663  neutrophil elastase-like isoform X1 [KO:K01327] [EC:3.4.21.37]
124512901  myeloperoxidase [KO:K10789] [EC:1.11.2.2]
124519153  actin, cytoplasmic 1 [KO:K05692]
124522513  actin, cytoplasmic 2 [KO:K05692]
124505439  LOW QUALITY PROTEIN: voltage-dependent anion-selective channel protein 1-like [KO:K05862]
124515603  voltage-dependent anion-selective channel protein 1 [KO:K05862]
124506927  voltage-dependent anion-selective channel protein 2 [KO:K15040]
124520533  voltage-dependent anion-selective channel protein 3 isoform X1 [KO:K15041]
124517976  LOW QUALITY PROTEIN: ADP/ATP translocase 2-like [KO:K05863]
124513873  ADP/ATP translocase 2 [KO:K05863]
124520964  ADP/ATP translocase 1 [KO:K05863]
124520991  ADP/ATP translocase 4 [KO:K05863]
124509313  ADP/ATP translocase 3 [KO:K05863]
124506936  peptidyl-prolyl cis-trans isomerase F, mitochondrial isoform X1 [KO:K09565] [EC:5.2.1.8]
124514649  protein-arginine deiminase type-4-like [KO:K24669] [EC:3.5.3.15]
124515442  high affinity immunoglobulin gamma Fc receptor I-like isoform X1 [KO:K06498]
124517946  integrin alpha-M-like isoform X1 [KO:K06461]
124526693  integrin beta-2-like [KO:K06464]
124517784  integrin alpha-L-like isoform X1 [KO:K05718]
124501257  C-type lectin domain family 7 member A-like isoform X1 [KO:K10074]
124504000  proto-oncogene tyrosine-protein kinase Src [KO:K05704] [EC:2.7.10.2]
124503791  1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4-like [KO:K05858] [EC:3.1.4.11]
124503878  1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 [KO:K05858] [EC:3.1.4.11]
124505119  1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 [KO:K05858] [EC:3.1.4.11]
124508712  1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 isoform X1 [KO:K05858] [EC:3.1.4.11]
124503060  1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 isoform X1 [KO:K01116] [EC:3.1.4.11]
124511524  1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2 isoform X1 [KO:K05859] [EC:3.1.4.11]
124513500  protein kinase C alpha type isoform X1 [KO:K02677] [EC:2.7.11.13]
124517730  protein kinase C beta type isoform X1 [KO:K19662] [EC:2.7.11.13]
124527789  protein kinase C gamma type [KO:K19663] [EC:2.7.11.13]
124524150  ubiquitin-like modifier-activating enzyme ATG7 isoform X1 [KO:K08337]
124510835  N-formyl peptide receptor 2-like isoform X1 [KO:K04173]
124525968  phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
124527077  phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
124514827  phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
124517840  phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
124514527  phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
124523730  phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
124510270  RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
124511119  RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
124512474  RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
124514798  serine/threonine-protein kinase mTOR [KO:K07203] [EC:2.7.11.1]
124520800  nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
124504954  transcription factor p65 [KO:K04735]
124522820  complement C3-like [KO:K03990]
124522854  complement C3-like [KO:K03990]
124522856  complement C3-like [KO:K03990]
124522857  complement C3-like isoform X1 [KO:K03990]
124522858  complement C3-like [KO:K03990]
124523587  complement C3-like [KO:K03990]
124523589  complement C3-like [KO:K03990]
124523590  complement C3-like [KO:K03990]
124524010  complement C3-like [KO:K03990]
124510073  complement component receptor 1-like protein [KO:K04011]
124526637  complement C5-like [KO:K03994]
124510980  C5a anaphylatoxin chemotactic receptor 1-like isoform X1 [KO:K04010]
124511302  high mobility group protein B1 [KO:K10802]
124501547  LOW QUALITY PROTEIN: high mobility group protein B1-like [KO:K10802]
124520186  toll-like receptor 2 [KO:K10159]
124503507  toll-like receptor 4 [KO:K10160]
124528014  mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
124528088  mitogen-activated protein kinase 13 isoform X1 [KO:K04441] [EC:2.7.11.24]
124501588  mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24]
124502315  mitogen-activated protein kinase 11 isoform X1 [KO:K04441] [EC:2.7.11.24]
124522131  integrin alpha-IIb-like [KO:K06476]
124513557  integrin beta-3 [KO:K06493]
124519948  fibrinogen alpha chain-like [KO:K03903]
124520896  fibrinogen beta chain [KO:K03904]
124520645  fibrinogen gamma chain isoform X1 [KO:K03905]
124519559  platelet glycoprotein Ib alpha chain-like [KO:K06261]
124502187  von Willebrand factor [KO:K03900]
124510233  P-selectin-like isoform X1 [KO:K06496]
124518462  P-selectin glycoprotein ligand 1-like isoform X1 [KO:K06544]
124529037  advanced glycosylation end product-specific receptor-like isoform X1 [KO:K19722]
124505860  caspase-1 isoform X1 [KO:K04394] [EC:3.4.22.57 3.4.22.64]
124507856  gasdermin-D-like [KO:K20917]
124521243  histone acetyltransferase type B catalytic subunit-like [KO:K11303] [EC:2.3.1.48]
124516008  histone acetyltransferase type B catalytic subunit [KO:K11303] [EC:2.3.1.48]
124505332  histone H2AX [KO:K11251]
124519941  histone H2A type 3 [KO:K11251]
124505905  core histone macro-H2A.2 [KO:K11251]
124527613  histone H2A-Bbd type 2/3-like [KO:K11251]
124527614  histone H2A-Bbd type 2/3-like [KO:K11251]
124527634  histone H2A-Bbd type 2/3-like [KO:K11251]
124520857  histone H2A.Z [KO:K11251]
124528469  histone H2A type 1-H-like [KO:K11251]
124528470  histone H2A type 1-E [KO:K11251]
124528471  histone H2A type 1-E [KO:K11251]
124528472  histone H2A type 1-E [KO:K11251]
124528473  histone H2A type 1-E [KO:K11251]
124528475  histone H2A type 1-E [KO:K11251]
124528476  histone H2A type 1-B [KO:K11251]
124528477  histone H2A type 1-H-like [KO:K11251]
124528478  histone H2A type 1-E [KO:K11251]
124528480  histone H2A type 1-B [KO:K11251]
124528481  histone H2A type 1-E-like [KO:K11251]
124528482  histone H2A type 1-E-like [KO:K11251]
124528560  histone H2A type 1-H-like [KO:K11251]
124514741  histone H2A type 2-B [KO:K11251]
124514742  histone H2A type 2-C [KO:K11251]
124515218  histone H2A type 2-A [KO:K11251]
124529233  histone H2A type 1-H-like [KO:K11251]
124515853  core histone macro-H2A.1 isoform X1 [KO:K11251]
124502417  histone H2A.J [KO:K11251]
124509442  histone H2A-Bbd type 1-like [KO:K11251]
124516373  histone H2A type 2-A [KO:K11251]
124509671  histone H2A-Bbd type 1-like [KO:K11251]
124509672  histone H2A-Bbd type 1-like [KO:K11251]
124509681  histone H2A-Bbd type 1-like [KO:K11251]
124523951  histone H2A.V isoform X1 [KO:K11251]
124510558  histone H2B subacrosomal variant-like [KO:K11252]
124519855  histone H2B type 3-B [KO:K11252]
124528453  histone H2B type 1-B-like [KO:K11252]
124528463  histone H2B type 1-K-like [KO:K11252]
124528483  histone H2B type 1-C/E/F/G/I [KO:K11252]
124528484  histone H2B type 1-M [KO:K11252]
124528485  histone H2B type 1-M [KO:K11252]
124528486  histone H2B type 1-C/E/F/G/I [KO:K11252]
124528487  histone H2B type 1-J [KO:K11252]
124528488  histone H2B type 1-K [KO:K11252]
124528489  histone H2B type 1-K [KO:K11252]
124528490  histone H2B type 1-C/E/F/G/I [KO:K11252]
124528492  histone H2B type 1-C/E/F/G/I [KO:K11252]
124528493  histone H2B type 1-C/E/F/G/I [KO:K11252]
124528494  histone H2B type 1-C/E/F/G/I [KO:K11252]
124528496  histone H2B type 1-C/E/F/G/I [KO:K11252]
124528497  histone H2B type 1-C/E/F/G/I [KO:K11252]
124528498  histone H2B type 1-C/E/F/G/I [KO:K11252]
124528499  histone H2B type 1-C/E/F/G/I [KO:K11252]
124514743  histone H2B type 2-E [KO:K11252]
124528683  histone H2B type 1-A [KO:K11252]
124515219  histone H2B type 2-E-like [KO:K11252]
124529019  histone H2B type 1-A-like [KO:K11252]
124516375  histone H2B type 2-F [KO:K11252]
124516376  histone H2B type 2-E-like [KO:K11252]
124523789  histone H2B type 2-K1 [KO:K11252]
124529236  uncharacterized protein LOC124529236 [KO:K11253]
124529238  uncharacterized protein LOC124529238 [KO:K11253]
124510297  histone H3.3A [KO:K11253]
124512311  histone H3.3A-like [KO:K11253]
124513410  histone H3.3A [KO:K11253]
124528462  histone H3.3-like [KO:K11253]
124528464  histone H3.1 [KO:K11253]
124528465  histone H3.1 [KO:K11253]
124528466  histone H3.1 [KO:K11253]
124528467  histone H3.1 [KO:K11253]
124528468  histone H3.1 [KO:K11253]
124528513  histone H3.1-like [KO:K11253]
124529235  histone H3.1-like [KO:K11253]
124528271  histone deacetylase 2 [KO:K06067] [EC:3.5.1.98]
124514885  histone deacetylase 1 isoform X1 [KO:K06067] [EC:3.5.1.98]
124516851  histone deacetylase 3 isoform X1 [KO:K11404] [EC:3.5.1.98]
124522083  histone deacetylase 5 isoform X1 [KO:K11406] [EC:3.5.1.98]
124516439  histone deacetylase 4 isoform X1 [KO:K11406] [EC:3.5.1.98]
124509514  histone deacetylase 6-like isoform X1 [KO:K11407] [EC:3.5.1.98]
124501050  histone deacetylase 7 isoform X1 [KO:K11408] [EC:3.5.1.98]
124521560  histone deacetylase 8 isoform X1 [KO:K11405] [EC:3.5.1.98]
124523093  histone deacetylase 9 isoform X1 [KO:K11409] [EC:3.5.1.98]
124501803  polyamine deacetylase HDAC10-like isoform X1 [KO:K18671] [EC:3.5.1.98]
124523920  histone deacetylase 11 [KO:K11418] [EC:3.5.1.98]
124508203  cathepsin G-like [KO:K01319] [EC:3.4.21.20]
124523702  cathelicidin antimicrobial peptide-like [KO:K13916]
124520273  H(+)/Cl(-) exchange transporter 3 isoform X1 [KO:K05012]
124509340  H(+)/Cl(-) exchange transporter 4 isoform X1 [KO:K05012]
124509540  H(+)/Cl(-) exchange transporter 5 [KO:K05012]
124508555  aquaporin-9 isoform X1 [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
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
lruf04010  MAPK signaling pathway
lruf04020  Calcium signaling pathway
lruf04140  Autophagy - animal
lruf04151  PI3K-Akt signaling pathway
lruf04610  Complement and coagulation cascades
lruf04611  Platelet activation
lruf04620  Toll-like receptor signaling pathway
lruf04621  NOD-like receptor signaling pathway
lruf04666  Fc gamma R-mediated phagocytosis
KO pathway
ko04613   
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