Entry Name Neutrophil extracellular trap formation
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 systemBRITE hierarchy
Pathway map ko04613 Neutrophil extracellular trap formation
Orthology K00922 PIK3CA_B_D; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha/beta/delta [EC:2.7.1.153 ]
K01116 PLCG1; phosphatidylinositol phospholipase C, gamma-1 [EC:3.1.4.11 ]
K02580 NFKB1; nuclear factor NF-kappa-B p105 subunit
K02649 PIK3R1_2_3; phosphoinositide-3-kinase regulatory subunit alpha/beta/delta
K03900 VWF; von Willebrand factor
K03903 FGA; fibrinogen alpha chain
K03904 FGB; fibrinogen beta chain
K03905 FGG; fibrinogen gamma chain
K03990 C3; complement component 3
K03994 C5; complement component 5
K04010 C5AR1, CD88; C5a anaphylatoxin chemotactic receptor 1
K04011 CR1, CD35; complement component (3b/4b) receptor 1
K04172 FPR1; formyl peptide receptor 1
K04173 FPRL; formyl peptide receptor-like
K04366 RAF1; RAF proto-oncogene serine/threonine-protein kinase [EC:2.7.11.1 ]
K04368 MAP2K1, MEK1; mitogen-activated protein kinase kinase 1 [EC:2.7.12.2 ]
K04369 MAP2K2, MEK2; mitogen-activated protein kinase kinase 2 [EC:2.7.12.2 ]
K04392 RAC1; Ras-related C3 botulinum toxin substrate 1
K04427 MAP3K7, TAK1; mitogen-activated protein kinase kinase kinase 7 [EC:2.7.11.25 ]
K04735 RELA; transcription factor p65
K05012 CLCN3_4_5; chloride channel 3/4/5
K05404 TLR7; toll-like receptor 7
K05692 ACTB_G1; actin beta/gamma 1
K05718 ITGAL, CD11a; integrin alpha L
K05859 PLCG2; phosphatidylinositol phospholipase C, gamma-2 [EC:3.1.4.11 ]
K05862 VDAC1; voltage-dependent anion channel protein 1
K05863 SLC25A4S, ANT; solute carrier family 25 (mitochondrial adenine nucleotide translocator), member 4/5/6/31
K06261 GP1BA, CD42b; platelet glycoprotein Ib alpha chain
K06461 ITGAM, CD11b; integrin alpha M
K06463 FCGR3, CD16; low affinity immunoglobulin gamma Fc receptor III
K06464 ITGB2, CD18; integrin beta 2
K06472 FCGR2A, CD32; low affinity immunoglobulin gamma Fc receptor II-a
K06476 ITGA2B, CD41; integrin alpha 2B
K06493 ITGB3, CD61; integrin beta 3
K06496 SELP, CD62P; selectin, platelet
K06498 FCGR1A, CD64; high affinity immunoglobulin gamma Fc receptor I
K06544 SELPLG, CD162; selectin P ligand
K06740 SIGLEC9, CD329; sialic acid binding Ig-like lectin 9
K06856 IGH; immunoglobulin heavy chain
K07203 MTOR, FRAP, TOR; serine/threonine-protein kinase mTOR [EC:2.7.11.1 ]
K07860 RAC2; Ras-related C3 botulinum toxin substrate 2
K08009 CYBA, P22PHOX; cytochrome b-245, alpha polypeptide
K08010 NCF2, P67PHOX; neutrophil cytosolic factor 2
K08011 NCF1, P47PHOX; neutrophil cytosolic factor 1
K08012 NCF4, P40PHOX; neutrophil cytosolic factor 4
K08337 ATG7; ubiquitin-like modifier-activating enzyme ATG7
K09565 PPIF; peptidyl-prolyl isomerase F (cyclophilin D) [EC:5.2.1.8 ]
K10074 CLEC7A, DECTIN1, CD369; C-type lectin domain family 7 member A
K10159 TLR2, CD282; toll-like receptor 2
K10160 TLR4, CD284; toll-like receptor 4
K10170 TLR8, CD288; toll-like receptor 8
K10802 HMGB1; high mobility group protein B1
K13916 CAMP, LL37; cathelicidin antimicrobial peptide
K15040 VDAC2; voltage-dependent anion channel protein 2
K15041 VDAC3; voltage-dependent anion channel protein 3
K19722 AGER, RAGE; receptor for advanced glycosylation end products
K21421 NOX2, GP91, CYBB; NADPH oxidase 2 [EC:1.-.-.-]
K24669 PADI4, PAD4; protein-arginine deiminase 4
Compound 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 Reference Authors Sorvillo N, Cherpokova D, Martinod K, Wagner DD
Title Extracellular DNA NET-Works With Dire Consequences for Health.
Journal Reference Authors Papayannopoulos V
Title Neutrophil extracellular traps in immunity and disease.
Journal Reference Authors Liu FC, Chuang YH, Tsai YF, Yu HP
Title Role of neutrophil extracellular traps following injury.
Journal 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 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 Reference Authors Honda M, Kubes P
Title Neutrophils and neutrophil extracellular traps in the liver and gastrointestinal system.
Journal Reference Authors Hamam HJ, Palaniyar N
Title Post-Translational Modifications in NETosis and NETs-Mediated Diseases.
Journal Reference Authors Burgener SS, Schroder K
Title Neutrophil Extracellular Traps in Host Defense.
Journal Reference Authors Vorobjeva NV, Chernyak BV
Title NETosis: Molecular Mechanisms, Role in Physiology and Pathology.
Journal Reference Authors Ravindran M, Khan MA, Palaniyar N
Title Neutrophil Extracellular Trap Formation: Physiology, Pathology, and Pharmacology.
Journal Reference Authors Jorch SK, Kubes P
Title An emerging role for neutrophil extracellular traps in noninfectious disease.
Journal 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 Reference Authors Kim SJ, Jenne CN
Title Role of platelets in neutrophil extracellular trap (NET) production and tissue injury.
Journal Reference Authors de Bont CM, Boelens WC, Pruijn GJM
Title NETosis, complement, and coagulation: a triangular relationship.
Journal 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 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 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 Reference Authors Vorobjeva NV, Pinegin BV
Title Neutrophil extracellular traps: mechanisms of formation and role in health and disease.
Journal 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 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 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 Reference Authors Schonrich G, Raftery MJ
Title Neutrophil Extracellular Traps Go Viral.
Journal 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 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 ko04610 Complement and coagulation cascades
ko04620 Toll-like receptor signaling pathway
ko04621 NOD-like receptor signaling pathway
ko04666 Fc gamma R-mediated phagocytosis
