KEGG   PATHWAY: aml04613
Entry
aml04613                    Pathway                                
Name
Neutrophil extracellular trap formation - Ailuropoda melanoleuca (giant panda)
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
aml04613  Neutrophil extracellular trap formation
aml04613

Organism
Ailuropoda melanoleuca (giant panda) [GN:aml]
Gene
100463612  [KO:K11251]
100463617  [KO:K11251]
100463625  VDAC1; voltage-dependent anion-selective channel protein 1 [KO:K05862]
100463775  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
100464009  ITGAL; integrin alpha-L isoform X1 [KO:K05718]
100464085  SLC25A31; ADP/ATP translocase 4 [KO:K05863]
100464112  [KO:K11252]
100464188  [KO:K11252]
100464367  [KO:K11254]
100464611  [KO:K11253]
100464863  [KO:K11251]
100464921  [KO:K04394] [EC:3.4.22.57 3.4.22.64]
100465110  [KO:K11254]
100465129  TLR2; toll-like receptor 2 [KO:K10159]
100465190  [KO:K11251]
100465223  MAPK13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
100465232  PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 [KO:K05858] [EC:3.1.4.11]
100465442  [KO:K11252]
100465476  MAPK14; mitogen-activated protein kinase 14 isoform X3 [KO:K04441] [EC:2.7.11.24]
100465507  VDAC2; voltage-dependent anion-selective channel protein 2 [KO:K15040]
100465648  RAC1; ras-related C3 botulinum toxin substrate 1 [KO:K04392]
100465694  [KO:K11251]
100465700  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
100465793  AKT1; RAC-alpha serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
100465943  [KO:K11254]
100465958  [KO:K11251]
100466132  ACTG1; actin, cytoplasmic 2 [KO:K05692]
100466134  HDAC3; histone deacetylase 3 [KO:K11404] [EC:3.5.1.98]
100466140  FGB; fibrinogen beta chain [KO:K03904]
100466194  [KO:K11251]
100466373  [KO:K11251]
100466387  FGG; fibrinogen gamma chain isoform X2 [KO:K03905]
100466506  MAP3K7; mitogen-activated protein kinase kinase kinase 7 isoform X1 [KO:K04427] [EC:2.7.11.25]
100466534  ATG7; ubiquitin-like modifier-activating enzyme ATG7 isoform X1 [KO:K08337]
100466624  [KO:K11252]
100466688  [KO:K11251]
100466870  [KO:K11252]
100466888  [KO:K11251]
100466939  [KO:K11254]
100467119  [KO:K11252]
100467120  [KO:K06261]
100467125  [KO:K11252]
100467144  TLR8; toll-like receptor 8 [KO:K10170]
100467187  [KO:K11251]
100467398  TLR7; toll-like receptor 7 [KO:K05404]
100467440  [KO:K11252]
100467479  CLCN5; H(+)/Cl(-) exchange transporter 5 isoform X1 [KO:K05012]
100467516  [KO:K11251]
100467802  [KO:K10802]
100467827  SELP; P-selectin isoform X3 [KO:K06496]
100467878  [KO:K11252]
100467906  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
100467916  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
100468125  [KO:K11253]
100468151  [KO:K11252]
100468223  [KO:K21421] [EC:1.-.-.-]
100468228  NCF4; neutrophil cytosol factor 4 [KO:K08012]
100468249  HDAC5; histone deacetylase 5 isoform X1 [KO:K11406] [EC:3.5.1.98]
100468340  AQP9; aquaporin-9 isoform X1 [KO:K09877]
100468404  [KO:K11252]
100468629  [KO:K11251]
100468651  CLCN4; H(+)/Cl(-) exchange transporter 4 isoform X2 [KO:K05012]
100468710  VWF; von Willebrand factor [KO:K03900]
100468763  AKT2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
100468878  [KO:K11252]
100468902  HDAC9; histone deacetylase 9 isoform X11 [KO:K11409] [EC:3.5.1.98]
100468944  [KO:K11254]
100469194  [KO:K11252]
100469401  FGA; fibrinogen alpha chain [KO:K03903]
100469449  [KO:K11252]
100469507  SLC25A6; ADP/ATP translocase 3 [KO:K05863]
100469737  RAC2; ras-related C3 botulinum toxin substrate 2 [KO:K07860]
100470035  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
100470118  C5AR1; C5a anaphylatoxin chemotactic receptor 1 [KO:K04010]
100470211  [KO:K11252]
100470602  [KO:K11253]
100470763  VDAC3; voltage-dependent anion-selective channel protein 3 isoform X1 [KO:K15041]
100470965  [KO:K11252]
100471070  [KO:K11253]
100471122  MTOR; serine/threonine-protein kinase mTOR [KO:K07203] [EC:2.7.11.1]
100471129  [KO:K24669]
100471319  [KO:K11254]
100471469  [KO:K11252]
100471714  [KO:K11253]
100471819  FCGR1A; high affinity immunoglobulin gamma Fc receptor I [KO:K06498]
100472388  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
100472549  C3; complement C3 [KO:K03990]
100472606  NCF1; neutrophil cytosol factor 1 [KO:K08011]
100472815  TLR4; toll-like receptor 4 isoform X1 [KO:K10160]
100472895  MPO; myeloperoxidase [KO:K10789] [EC:1.11.2.2]
100473508  SLC25A4; ADP/ATP translocase 1 [KO:K05863]
100473720  CLEC7A; C-type lectin domain family 7 member A isoform X2 [KO:K10074]
100474271  SRC; proto-oncogene tyrosine-protein kinase Src isoform X1 [KO:K05704] [EC:2.7.10.2]
100474458  HDAC7; histone deacetylase 7 isoform X1 [KO:K11408] [EC:3.5.1.98]
100474543  SYK; tyrosine-protein kinase SYK isoform X1 [KO:K05855] [EC:2.7.10.2]
100474779  PLCB2; LOW QUALITY PROTEIN: 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 [KO:K05858] [EC:3.1.4.11]
100475291  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
100475340  [KO:K06461]
100476256  ITGB3; integrin beta-3 [KO:K06493]
100476651  SELPLG; P-selectin glycoprotein ligand 1 [KO:K06544]
100476732  SLC25A5; ADP/ATP translocase 2 [KO:K05863]
100476818  HDAC11; histone deacetylase 11 isoform X2 [KO:K11418] [EC:3.5.1.98]
100476832  NCF2; neutrophil cytosol factor 2 [KO:K08010]
100476851  [KO:K10802]
100476918  [KO:K11253]
100476997  CAMP; cathelicidin antimicrobial peptide [KO:K13916]
100477105  AGER; advanced glycosylation end product-specific receptor isoform X1 [KO:K19722]
100477187  [KO:K11251]
100477326  PRKCA; protein kinase C alpha type [KO:K02677] [EC:2.7.11.13]
100477725  HDAC1; histone deacetylase 1 isoform X1 [KO:K06067] [EC:3.5.1.98]
100478007  PRKCB; protein kinase C beta type isoform X2 [KO:K19662] [EC:2.7.11.13]
100478013  [KO:K11251]
100478039  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
100478424  HDAC2; histone deacetylase 2 [KO:K06067] [EC:3.5.1.98]
100478591  HDAC4; histone deacetylase 4 [KO:K11406] [EC:3.5.1.98]
100478725  HDAC6; histone deacetylase 6 isoform X1 [KO:K11407] [EC:3.5.1.98]
100479294  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
100479502  [KO:K11251]
100479580  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:2.7.1.153]
100479700  [KO:K11251]
100479771  [KO:K11254]
100479978  HDAC10; polyamine deacetylase HDAC10 isoform X1 [KO:K18671] [EC:3.5.1.98]
100480024  [KO:K11253]
100480123  FPR2; N-formyl peptide receptor 2 [KO:K04173]
100480158  RELA; transcription factor p65 isoform X1 [KO:K04735]
100480199  [KO:K04011]
100480235  MAPK12; mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24]
100480414  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
100480483  MAPK11; mitogen-activated protein kinase 11 [KO:K04441] [EC:2.7.11.24]
100480586  PLCG1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 isoform X2 [KO:K01116] [EC:3.1.4.11]
100480603  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 [KO:K05858] [EC:3.1.4.11]
100480623  HDAC8; histone deacetylase 8 isoform X8 [KO:K11405] [EC:3.5.1.98]
100480781  [KO:K11251]
100481255  [KO:K11252]
100481285  [KO:K11254]
100481535  [KO:K11252]
100481603  PPIF; peptidyl-prolyl cis-trans isomerase F, mitochondrial [KO:K09565] [EC:5.2.1.8]
100481755  PLCB1; LOW QUALITY PROTEIN: 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 [KO:K05858] [EC:3.1.4.11]
100481913  CLCN3; H(+)/Cl(-) exchange transporter 3 isoform X2 [KO:K05012]
100481923  [KO:K06463]
100481966  [KO:K11252]
100481994  PLCG2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2 isoform X1 [KO:K05859] [EC:3.1.4.11]
100482073  [KO:K11251]
100482255  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
100482289  [KO:K11254]
100482301  [KO:K11252]
100482328  [KO:K11251]
100482539  [KO:K11254]
100482551  [KO:K11251]
100482789  [KO:K11253]
100482800  [KO:K11253]
100482816  [KO:K11251]
100482979  [KO:K08009]
100483168  C5; complement C5 [KO:K03994]
100483277  HAT1; histone acetyltransferase type B catalytic subunit isoform X1 [KO:K11303] [EC:2.3.1.48]
100483293  [KO:K11251]
100483305  [KO:K11252]
100483542  [KO:K11252]
100483791  [KO:K11251]
100483828  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
100484046  [KO:K11252]
100484185  ITGA2B; integrin alpha-IIb [KO:K06476]
100484264  ITGB2; integrin beta-2 isoform X1 [KO:K06464]
100484366  GSDMD; gasdermin-D isoform X1 [KO:K20917]
100484719  PRKCG; protein kinase C gamma type isoform X1 [KO:K19663] [EC:2.7.11.13]
100484819  [KO:K11251]
105234312  [KO:K01327] [EC:3.4.21.37]
105234948  [KO:K11252]
105235968  [KO:K11252]
105238125  [KO:K11251]
105241088  [KO:K11251]
109490384  [KO:K11251]
109490817  [KO:K11253]
109490984  [KO:K21421] [EC:1.-.-.-]
109491083  [KO:K11252]
117794999  [KO:K11251]
117795041  [KO:K11254]
117797265  [KO:K01319] [EC:3.4.21.20]
117799792  [KO:K05863]
117800125  [KO:K05692]
117800181  [KO:K05692]
117800361  [KO:K05692]
117800408  [KO:K05692]
117802187  [KO:K11253]
117802188  [KO:K11253]
117802189  [KO:K11253]
117802190  [KO:K11254]
117802192  [KO:K11253]
117802250  [KO:K11254]
117803471  [KO:K11253]
117804403  [KO:K11251]
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
aml04010  MAPK signaling pathway
aml04020  Calcium signaling pathway
aml04140  Autophagy - animal
aml04151  PI3K-Akt signaling pathway
aml04610  Complement and coagulation cascades
aml04611  Platelet activation
aml04620  Toll-like receptor signaling pathway
aml04621  NOD-like receptor signaling pathway
aml04666  Fc gamma R-mediated phagosome formation
KO pathway
ko04613   

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