Generic placeholder image

Current Rheumatology Reviews


ISSN (Print): 1573-3971
ISSN (Online): 1875-6360

Review Article

Ambiguities in Neutrophil Extracellular Traps. Ongoing Concepts and Potential Biomarkers for Rheumatoid Arthritis: A Narrative Review

Author(s): Andrei S. Trofimenko*, Elena E. Mozgovaya, Svetlana A. Bedina and Alexander A. Spasov

Volume 17 , Issue 3 , 2021

Published on: 21 December, 2020

Page: [283 - 293] Pages: 11

DOI: 10.2174/1573397116666201221113100

Price: $65


Objective: This study aims to provide consolidation of current research findings as well as the most important concepts regarding neutrophil extracellular traps (NETs) in rheumatoid arthritis.

Data Sources: Relevant publications from 2004 to 2018 were identified using PubMed, Web of Science, Scopus, and eLibrary databases. Primary search terms used were “neutrophil extracellular traps” or “NETs” in combination with “rheumatoid arthritis”.

Data Synthesis: NETs are distinctive structures promoting capture and non-phagocytic cleavage of foreign substances. NETs usually consist of thin chromatin fibers decorated with various molecules of granular, cytosolic, and cytoskeletal origin. NETosis can develop in two ways: either with neutrophil death or when the viability of the cell prolongs. ROS generation and pronounced protein citrullination are essential during the initial phase of NETs formation. NETosis is considered to have certain immunological consequences, including DAMPs-mediated signalling, proinflammatory cytokine secretion, and contact of extensively modified self and foreign epitopes with antigen-presenting cells. There are several putative pathogenetic links between NETosis, citrullination, neoepitope formation, and production of anticitrullined autoantibodies that can strongly influence rheumatoid arthritis progression. NET-induced vascular injury in rheumatoid arthritis can arise directly from NETs and indirectly through enhanced thrombosis and atherosclerosis.

Conclusion: NETs are currently estimated as a possible influential factor of rheumatoid arthritis initiation and/or progression, especially in the context of vascular involvement. NETs can also serve as a source of novel antigenic biomarkers for the diagnosis of rheumatoid arthritis.

Keywords: Neutrophil extracellular traps, NETosis, polymorphonuclear cells, rheumatoid arthritis, immunology, autoimmunity, anti-citrulline antibodies.

Graphical Abstract
Brinkmann V, Reichard U, Goosmann C, et al. Neutrophil extracellular traps kill bacteria. Science 2004; 303(5663): 1532-5.
[] [PMID: 15001782]
Steinberg BE, Grinstein S. Unconventional roles of the NADPH oxidase: signaling, ion homeostasis, and cell death. Sci STKE 2007; 2007(379): pe11.
[] [PMID: 17392241]
Yousefi S, Gold JA, Andina N, et al. Catapult-like release of mitochondrial DNA by eosinophils contributes to antibacterial defense. Nat Med 2008; 14(9): 949-53.
[] [PMID: 18690244]
von Köckritz-Blickwede M, Goldmann O, Thulin P, et al. Phagocytosis-independent antimicrobial activity of mast cells by means of extracellular trap formation. Blood 2008; 111(6): 3070-80.
[] [PMID: 18182576]
Chow OA, von Köckritz-Blickwede M, Bright AT, et al. Statins enhance formation of phagocyte extracellular traps. Cell Host Microbe 2010; 8(5): 445-54.
[] [PMID: 21075355]
Mayadas TN, Cullere X, Lowell CA. The multifaceted functions of neutrophils. Annu Rev Pathol 2014; 9: 181-218.
[] [PMID: 24050624]
Teng TS, Ji AL, Ji XY, Li YZ. Neutrophils and immunity: from bactericidal action to being conquered. J Immunol Res 2017; 2017: 9671604.
[] [PMID: 28299345]
Urban CF, Ermert D, Schmid M, et al. Neutrophil extracellular traps contain calprotectin, a cytosolic protein complex involved in host defense against Candida albicans. PLoS Pathog 2009; 5(10): e1000639.
[] [PMID: 19876394]
Borregaard N. Neutrophils, from marrow to microbes. Immunity 2010; 33(5): 657-70.
[] [PMID: 21094463]
O’Donoghue AJ, Jin Y, Knudsen GM, et al. Global substrate profiling of proteases in human neutrophil extracellular traps reveals consensus motif predominantly contributed by elastase. PLoS One 2013; 8(9): e75141.
Wright HL, Moots RJ, Edwards SW. The multifactorial role of neutrophils in rheumatoid arthritis. Nat Rev Rheumatol 2014; 10(10): 593-601.
[] [PMID: 24914698]
Vorobjeva NV, Pinegin BV. Neutrophil extracellular traps: mechanisms of formation and role in health and disease. Biochemistry (Mosc) 2014; 79(12): 1286-96.
[] [PMID: 25716722]
Brinkmann V, Zychlinsky A. Beneficial suicide: why neutrophils die to make NETs. Nat Rev Microbiol 2007; 5(8): 577-82.
[] [PMID: 17632569]
Pinegin B, Vorobjeva N, Pinegin V. Neutrophil extracellular traps and their role in the development of chronic inflammation and autoimmunity. Autoimmun Rev 2015; 14(7): 633-40.
[] [PMID: 25797532]
Papayannopoulos V, Zychlinsky A. NETs: a new strategy for using old weapons. Trends Immunol 2009; 30(11): 513-21.
[] [PMID: 19699684]
Parker H, Albrett AM, Kettle AJ, Winterbourn CC. Myeloperoxidase associated with neutrophil extracellular traps is active and mediates bacterial killing in the presence of hydrogen peroxide. J Leukoc Biol 2012; 91(3): 369-76.
[] [PMID: 22131345]
Bianchi M, Niemiec MJ, Siler U, Urban CF, Reichenbach J. Restoration of anti-Aspergillus defense by neutrophil extracellular traps in human chronic granulomatous disease after gene therapy is calprotectin-dependent. J Allergy Clin Immunol 2011; 127(5): 1243-52.e7.
[] [PMID: 21376380]
Wright TK, Gibson PG, Simpson JL, McDonald VM, Wood LG, Baines KJ. Neutrophil extracellular traps are associated with inflammation in chronic airway disease. Respirology 2016; 21(3): 467-75.
[] [PMID: 26804470]
Keshari RS, Jyoti A, Dubey M, et al. Cytokines induced neutrophil extracellular traps formation: implication for the inflammatory disease condition. PLoS One 2012; 7(10): e48111.
[] [PMID: 23110185]
Schorn C, Janko C, Latzko M, Chaurio R, Schett G, Herrmann M. Monosodium urate crystals induce extracellular DNA traps in neutrophils, eosinophils, and basophils but not in mononuclear cells. Front Immunol 2012; 3: 277.
[] [PMID: 22969769]
Guimarães-Costa AB, Nascimento MTC, Wardini AB, Pinto-da-Silva LH, Saraiva EM. ETosis: A microbicidal mechanism beyond cell death. J Parasitol Res 2012; 2012: 929743.
[] [PMID: 22536481]
Zawrotniak M, Rapala-Kozik M. Neutrophil extracellular traps (NETs) - formation and implications. Acta Biochim Pol 2013; 60(3): 277-84.
[] [PMID: 23819131]
Yalavarthi S, Gould TJ, Rao AN, et al. Release of neutrophil extracellular traps by neutrophils stimulated with antiphospholipid antibodies: a newly identified mechanism of thrombosis in the antiphospholipid syndrome. Arthritis Rheumatol 2015; 67(11): 2990-3003.
[] [PMID: 26097119]
Behnen M, Leschczyk C, Möller S, et al. Immobilized immune complexes induce neutrophil extracellular trap release by human neutrophil granulocytes via FcγRIIIB and Mac-1. J Immunol 2014; 193(4): 1954-65.
[] [PMID: 25024378]
Hoppenbrouwers T, Autar ASA, Sultan AR, et al. In vitro induction of NETosis: Comprehensive live imaging comparison and systematic review. PLoS One 2017; 12(5): e0176472.
[] [PMID: 28486563]
Yipp BG, Kubes P. NETosis: how vital is it? Blood 2013; 122(16): 2784-94.
[] [PMID: 24009232]
Yang H, Biermann MH, Brauner JM, Liu Y, Zhao Y, Herrmann M. New insights into neutrophil extracellular traps: mechanisms of formation and role in inflammation. Front Immunol 2016; 7: 302.
[] [PMID: 27570525]
Gupta S, Chan DW, Zaal KJ, Kaplan MJ. A high-throughput real-time imaging technique to quantify NETosis and distinguish mechanisms of cell death in human neutrophils. J Immunol 2018; 200(2): 869-79.
[] [PMID: 29196457]
Rochael NC, Guimarães-Costa AB, Nascimento MT, et al. Classical ROS-dependent and early/rapid ROS-independent release of Neutrophil Extracellular Traps triggered by Leishmania parasites. Sci Rep 2015; 5:
[] [PMID: 26673780]
Khan MA, Philip LM, Cheung G, et al. Regulating NETosis: Increasing pH promotes NADPH oxidase-dependent NETosis. Front Med (Lausanne) 2018; 5: 10.3389/fmed.2018.00019/full.
[] [PMID: 29487850]
Wang Y, Li M, Stadler S, et al. Histone hypercitrullination mediates chromatin decondensation and neutrophil extracellular trap formation. J Cell Biol 2009; 184(2): 205-13.
[] [PMID: 19153223]
Leshner M, Wang S, Lewis C, et al. PAD4 mediated histone hypercitrullination induces heterochromatin decondensation and chromatin unfolding to form neutrophil extracellular trap-like structures. Front Immunol 2012; 3: 10.3389/fimmu.2012.00307/full.
[] [PMID: 23060885]
Muller S, Radic M. Citrullinated autoantigens: from diagnostic markers to pathogenetic mechanisms. Clin Rev Allergy Immunol 2015; 49(2): 232-9.
[] [PMID: 25355199]
Pilsczek FH, Salina D, Poon KK, et al. A novel mechanism of rapid nuclear neutrophil extracellular trap formation in response to Staphylococcus aureus. J Immunol 2010; 185(12): 7413-25.
[] [PMID: 21098229]
Yousefi S, Mihalache C, Kozlowski E, Schmid I, Simon HU. Viable neutrophils release mitochondrial DNA to form neutrophil extracellular traps. Cell Death Differ 2009; 16(11): 1438-44.
[] [PMID: 19609275]
Yousefi S, Morshed M, Amini P, et al. Basophils exhibit antibacterial activity through extracellular trap formation. Allergy 2015; 70(9): 1184-8.
[] [PMID: 26043360]
Berthelot JM, Le Goff B, Neel A, Maugars Y, Hamidou M. NETosis: At the crossroads of rheumatoid arthritis, lupus, and vasculitis. Joint Bone Spine 2017; 84(3): 255-62.
[] [PMID: 27426444]
Söderberg D, Segelmark M. Neutrophil extracellular traps in vasculitis, friend or foe? Curr Opin Rheumatol 2018; 30(1): 16-23.
[] [PMID: 28957962]
McDonald B, Davis RP, Kim SJ, et al. Platelets and neutrophil extracellular traps collaborate to promote intravascular coagulation during sepsis in mice. Blood 2017; 129(10): 1357-67.
[] [PMID: 28073784]
Yang S, Qi H, Kan K, et al. neutrophil extracellular traps promote hypercoagulability in patients with sepsis. Shock 2017; 47(2): 132-9.
[] [PMID: 27617671]
Kazzaz NM, Sule G, Knight JS. Intercellular interactions as regulators of NETosis. Front Immunol 2016; 7: 10.3389/fimmu.2016.00453/full.
[] [PMID: 27895638]
Doster RS, Rogers LM, Gaddy JA, Aronoff DM. Macrophage extracellular traps: A scoping review. J Innate Immun 2018; 10(1): 3-13.
[] [PMID: 28988241]
Honda M, Kubes P. Neutrophils and neutrophil extracellular traps in the liver and gastrointestinal system. Nat Rev Gastroenterol Hepatol
Stephan A, Fabri M. The NET, the trap and the pathogen: neutrophil extracellular traps in cutaneous immunity. Exp Dermatol 2015; 24(3): 161-6.
[] [PMID: 25421224]
Zhao ML, Chi H, Sun L. Neutrophil extracellular traps of Cynoglossus semilaevis: Production characteristics and antibacterial effect. Front Immunol 2017; 8: 290.
[] [PMID: 28382034]
Hakkim A, Fürnrohr BG, Amann K, et al. Impairment of neutrophil extracellular trap degradation is associated with lupus nephritis. Proc Natl Acad Sci USA 2010; 107(21): 9813-8.
[] [PMID: 20439745]
Kobayashi Y. Neutrophil biology: an update. EXCLI J 2015; 14: 220-7.
[PMID: 26600743]
Nakazawa D, Shida H, Kusunoki Y, et al. The responses of macrophages in interaction with neutrophils that undergo NETosis. J Autoimmun 2016; 67: 19-28.
[] [PMID: 26347075]
Farrera C, Fadeel B. Macrophage clearance of neutrophil extracellular traps is a silent process. J Immunol 2013; 191(5): 2647-56.
[] [PMID: 23904163]
Vénéreau E, Ceriotti C, Bianchi ME. DAMPs from cell death to new life. Front Immunol 2015; 6: 422.
[] [PMID: 26347745]
Magna M, Pisetsky DS. The alarmin properties of DNA and DNA-associated nuclear proteins. Clin Ther 2016; 38(5): 1029-41.
[] [PMID: 27021604]
Yipp BG, Petri B, Salina D, et al. Infection-induced NETosis is a dynamic process involving neutrophil multitasking in vivo. Nat Med 2012; 18(9): 1386-93.
[] [PMID: 22922410]
Theofilopoulos AN, Kono DH, Beutler B, Baccala R. Intracellular nucleic acid sensors and autoimmunity. J Interferon Cytokine Res 2011; 31(12): 867-86.
[] [PMID: 22029446]
Kang R, Tang D. What is the pathobiology of inflammation to cell death? Apoptosis, necrosis, necroptosis, autophagic cell death, pyroptosis, and NETosis.Autophagy networks in inflammation. Cham: Springer 2016; pp. 81-106.
Kumar S, Calianese D, Birge RB. Efferocytosis of dying cells differentially modulate immunological outcomes in tumor microenvironment. Immunol Rev 2017; 280(1): 149-64.
[] [PMID: 29027226]
Kaczmarek A, Vandenabeele P, Krysko DV. Necroptosis: the release of damage-associated molecular patterns and its physiological relevance. Immunity 2013; 38(2): 209-23.
[] [PMID: 23438821]
Tang D, Kang R, Coyne CB, Zeh HJ, Lotze MT. PAMPs and DAMPs: signal 0s that spur autophagy and immunity. Immunol Rev 2012; 249(1): 158-75.
[] [PMID: 22889221]
Apostolova P, Zeiser R. The role of purine metabolites as DAMPs in acute graft-versus-host disease. Front Immunol 2016; 7:
[] [PMID: 27818661]
Lood C, Arve S, Ledbetter J, Elkon KB. TLR7/8 activation in neutrophils impairs immune complex phagocytosis through shedding of FcgRIIA. J Exp Med 2017; 214(7): 2103-19.
[] [PMID: 28606989]
Hu Z, Murakami T, Tamura H, et al. Neutrophil extracellular traps induce IL-1β production by macrophages in combination with lipopolysaccharide. Int J Mol Med 2017; 39(3): 549-58.
[] [PMID: 28204821]
Branzk N, Papayannopoulos V. Molecular mechanisms regulating NETosis in infection and disease. Semin Immunopathol 2013; 35(4): 513-30.
[] [PMID: 23732507]
Kawasaki T, Kawai T. Toll-like receptor signaling pathways. Front Immunol 2014; 5: 2014.00461/full.
[] [PMID: 25309543]
Lester SN, Li K. Toll-like receptors in antiviral innate immunity. J Mol Biol 2014; 426(6): 1246-64.
[] [PMID: 24316048]
Lange C, Csernok E, Moosig F, Holle JU. Immune stimulatory effects of neutrophil extracellular traps in granulomatosis with polyangiitis. Clin Exp Rheumatol 2017; 35(1)(Suppl. 103): 33-9.
[PMID: 28281454]
Poli C, Augusto JF, Dauvé J, et al. IL-26 confers proinflammatory properties to extracellular DNA. J Immunol 2017; 198(9): 3650-61.
[] [PMID: 28356384]
Khandpur R, Carmona-Rivera C, Vivekanandan-Giri A, et al. NETs are a source of citrullinated autoantigens and stimulate inflammatory responses in rheumatoid arthritis. Sci Transl Med 2013; 5(178): 178ra40.
[] [PMID: 23536012]
Thieblemont N, Wright HL, Edwards SW, Witko-Sarsat V. Human neutrophils in auto-immunity. Semin Immunol 2016; 28(2): 159-73.
[] [PMID: 27036091]
Proost P, Van Damme J, Opdenakker G. Leukocyte gelatinase B cleavage releases encephalitogens from human myelin basic protein. Biochem Biophys Res Commun 1993; 192(3): 1175-81.
[] [PMID: 7685161]
Descamps FJ, Van den Steen PE, Nelissen I, Van Damme J, Opdenakker G. Remnant epitopes generate autoimmunity: from rheumatoid arthritis and multiple sclerosis to diabetes. Adv Exp Med Biol 2003; 535: 69-77.
[] [PMID: 14714889]
Van den Steen PE, Grillet B, Opdenakker G. Gelatinase B participates in collagen II degradation and releases glycosylated remnant epitopes in rheumatoid arthritis. Adv Exp Med Biol 2005; 564: 45-55.
[] [PMID: 16400806]
Klareskog L, Amara K, Malmström V. Adaptive immunity in rheumatoid arthritis: anticitrulline and other antibodies in the pathogenesis of rheumatoid arthritis. Curr Opin Rheumatol 2014; 26(1): 72-9.
[] [PMID: 24257366]
Rethi B, Krishnamurthy A, Catrina AI. Rheumatoid arthritis: transition from systemic autoimmunity to joint inflammation and bone loss.Protein deimination in human health and disease. 2nd ed. Cham: Springer International Publishing 2017; pp. 85-97.
Nguyen H, James EA. Immune recognition of citrullinated epitopes. Immunology 2016; 149(2): 131-8.
[] [PMID: 27531825]
Eyre S, Bowes J, Diogo D, et al. Biologics in Rheumatoid Arthritis Genetics and Genomics Study Syndicate; Wellcome Trust Case Control Consortium. High-density genetic mapping identifies new susceptibility loci for rheumatoid arthritis. Nat Genet 2012; 44(12): 1336-40.
[] [PMID: 23143596]
Hill JA, Bell DA, Brintnell W, et al. Arthritis induced by posttranslationally modified (citrullinated) fibrinogen in DR4-IE transgenic mice. J Exp Med 2008; 205(4): 967-79.
[] [PMID: 18391064]
Scally SW, Petersen J, Law SC, et al. A molecular basis for the association of the HLA-DRB1 locus, citrullination, and rheumatoid arthritis. J Exp Med 2013; 210(12): 2569-82.
[] [PMID: 24190431]
Amara K, Steen J, Murray F, et al. Monoclonal IgG antibodies generated from joint-derived B cells of RA patients have a strong bias toward citrullinated autoantigen recognition. J Exp Med 2013; 210(3): 445-55.
[] [PMID: 23440041]
Sokolove J, Bromberg R, Deane KD, et al. Autoantibody epitope spreading in the pre-clinical phase predicts progression to rheumatoid arthritis. PLoS One 2012; 7(5): e35296.
[] [PMID: 22662108]
Brink M, Hansson M, Mathsson L, et al. Multiplex analyses of antibodies against citrullinated peptides in individuals prior to development of rheumatoid arthritis. Arthritis Rheum 2013; 65(4): 899-910.
[] [PMID: 23310951]
Chen HH, Huang N, Chen YM, et al. Association between a history of periodontitis and the risk of rheumatoid arthritis: a nationwide, population-based, case-control study. Ann Rheum Dis 2013; 72(7): 1206-11.
[] [PMID: 22941768]
György B, Tóth E, Tarcsa E, Falus A, Buzás EI. Citrullination: a posttranslational modification in health and disease. Int J Biochem Cell Biol 2006; 38(10): 1662-77.
[] [PMID: 16730216]
Anzilotti C, Pratesi F, Tommasi C, Migliorini P. Peptidylarginine deiminase 4 and citrullination in health and disease. Autoimmun Rev 2010; 9(3): 158-60.
[] [PMID: 19540364]
Lange S, Gallagher M, Kholia S, et al. Peptidylarginine deiminases – roles in cancer and neurodegeneration and possible avenues for therapeutic intervention via modulation of exosome and microvesicle (EMV) release? Int J Mol Sci 2017; 18(6): 1196.
[] [PMID: 28587234]
Jiang Z, Cui Y, Wang L, Zhao Y, Yan S, Chang X. Investigating citrullinated proteins in tumour cell lines. World J Surg Oncol 2013; 11: 260.
[] [PMID: 24099319]
Lazarus RC, Buonora JE, Flora MN, et al. Protein citrullination: a proposed mechanism for pathology in traumatic brain injury. Front Neurol 2015; 6: 204.
[] [PMID: 26441823]
Clancy KW, Weerapana E, Thompson PR. Detection and identification of protein citrullination in complex biological systems. Curr Opin Chem Biol 2016; 30: 1-6.
[] [PMID: 26517730]
Guo W, Zheng Y, Xu B, et al. Investigating the expression, effect and tumorigenic pathway of PADI2 in tumors. OncoTargets Ther 2017; 10: 1475-85.
[] [PMID: 28331341]
Karlaftis V, Perera S, Monagle P, Ignjatovic V. Importance of post-translational modifications on the function of key haemostatic proteins. Blood Coagul Fibrinolysis 2016; 27(1): 1-4.
[] [PMID: 26484638]
Makrygiannakis D, af Klint E, Lundberg IE, et al. Citrullination is an inflammation-dependent process. Ann Rheum Dis 2006; 65(9): 1219-22.
[] [PMID: 16540548]
Baka Z, György B, Géher P, Buzás EI, Falus A, Nagy G. Citrullination under physiological and pathological conditions. Joint Bone Spine 2012; 79(5): 431-6.
[] [PMID: 22366145]
Yang L, Tan D, Piao H. Myelin basic protein citrullination in multiple sclerosis: a potential therapeutic target for the pathology. Neurochem Res 2016; 41(8): 1845-56.
[] [PMID: 27097548]
Gudmann NS, Hansen NU, Jensen AC, Karsdal MA, Siebuhr AS. Biological relevance of citrullinations: diagnostic, prognostic and therapeutic options. Autoimmunity 2015; 48(2): 73-9.
[] [PMID: 25520183]
Skriner K, Adolph K, Jungblut PR, Burmester GR. Association of citrullinated proteins with synovial exosomes. Arthritis Rheum 2006; 54(12): 3809-14.
[] [PMID: 17133577]
Asaga H, Nakashima K, Senshu T, Ishigami A, Yamada M. Immunocytochemical localization of peptidylarginine deiminase in human eosinophils and neutrophils. J Leukoc Biol 2001; 70(1): 46-51.
[PMID: 11435484]
Foulquier C, Sebbag M, Clavel C, et al. Peptidyl arginine deiminase type 2 (PAD-2) and PAD-4 but not PAD-1, PAD-3, and PAD-6 are expressed in rheumatoid arthritis synovium in close association with tissue inflammation. Arthritis Rheum 2007; 56(11): 3541-53.
[] [PMID: 17968929]
Vossenaar ER, Radstake TR, van der Heijden A, et al. Expression and activity of citrullinating peptidylarginine deiminase enzymes in monocytes and macrophages. Ann Rheum Dis 2004; 63(4): 373-81.
[] [PMID: 15020330]
Spengler J, Lugonja B, Ytterberg AJ, et al. Release of active peptidyl arginine deiminases by neutrophils can explain production of extracellular citrullinated autoantigens in rheumatoid arthritis synovial fluid. Arthritis Rheumatol 2015; 67(12): 3135-45.
[] [PMID: 26245941]
Corsiero E, Bombardieri M, Carlotti E, et al. Single cell cloning and recombinant monoclonal antibodies generation from RA synovial B cells reveal frequent targeting of citrullinated histones of NETs. Ann Rheum Dis 2016; 75(10): 1866-75.
[] [PMID: 26659717]
Sur Chowdhury C, Giaglis S, Walker UA, Buser A, Hahn S, Hasler P. Enhanced neutrophil extracellular trap generation in rheumatoid arthritis: analysis of underlying signal transduction pathways and potential diagnostic utility. Arthritis Res Ther 2014; 16(3):
[] [PMID: 24928093]
Dwivedi N, Chang HH, Ho IC. Citrullination and neutrophil extracellular traps.Protein deimination in human health and disease. 2nd ed. Cham: Springer International Publishing 2017; pp. 137-59.
Romero V, Fert-Bober J, Nigrovic PA, et al. Immune-mediated pore-forming pathways induce cellular hypercitrullination and generate citrullinated autoantigens in rheumatoid arthritis. Sci Transl Med 2013; 5(209): 209ra150.
[] [PMID: 24174326]
Rohrbach AS, Hemmers S, Arandjelovic S, Corr M, Mowen KA. PAD4 is not essential for disease in the K/BxN murine autoantibody-mediated model of arthritis. Arthritis Res Ther 2012; 14(3): R104.
[] [PMID: 22551352]
Willis VC, Gizinski AM, Banda NK, et al. N-α-benzoyl-N5-(2-chloro-1-iminoethyl)-L-ornithine amide, a protein arginine deiminase inhibitor, reduces the severity of murine collagen-induced arthritis. J Immunol 2011; 186(7): 4396-404.
[] [PMID: 21346230]
Dwivedi N, Upadhyay J, Neeli I, et al. Felty’s syndrome autoantibodies bind to deiminated histones and neutrophil extracellular chromatin traps. Arthritis Rheum 2012; 64(4): 982-92.
[] [PMID: 22034172]
Laurent L, Clavel C, Lemaire O, et al. Fcγ receptor profile of monocytes and macrophages from rheumatoid arthritis patients and their response to immune complexes formed with autoantibodies to citrullinated proteins. Ann Rheum Dis 2011; 70(6): 1052-9.
[] [PMID: 21406456]
El Bannoudi H, Ioan-Facsinay A, Toes RE. Bridging autoantibodies and arthritis: the role of Fc receptors.Fc receptors. Heidelberg: Springer 2014; pp. 303-19.
Gertel S, Serre G, Shoenfeld Y, Amital H. Immune tolerance induction with multiepitope peptide derived from citrullinated autoantigens attenuates arthritis manifestations in adjuvant arthritis rats. J Immunol 2015; 194(12): 5674-80.
[] [PMID: 25964493]
Sokolove J, Johnson DS, Lahey LJ, et al. Rheumatoid factor as a potentiator of anti-citrullinated protein antibody-mediated inflammation in rheumatoid arthritis. Arthritis Rheumatol 2014; 66(4): 813-21.
[] [PMID: 24757134]
Neeli I, Khan SN, Radic M. Histone deimination as a response to inflammatory stimuli in neutrophils. J Immunol 2008; 180(3): 1895-902.
[] [PMID: 18209087]
Papadaki G, Kambas K, Choulaki C, et al. Neutrophil extracellular traps exacerbate Th1-mediated autoimmune responses in rheumatoid arthritis by promoting DC maturation. Eur J Immunol 2016; 46(11): 2542-54.
[] [PMID: 27585946]
Knight JS, Subramanian V, O’Dell AA, et al. Peptidylarginine deiminase inhibition disrupts NET formation and protects against kidney, skin and vascular disease in lupus-prone MRL/lpr mice. Ann Rheum Dis 2015; 74(12): 2199-206.
[] [PMID: 25104775]
Pieterse E, Rother N, Garsen M, et al. Neutrophil extracellular traps drive endothelial-to-mesenchymal transition. Arterioscler Thromb Vasc Biol 2017; 37(7): 1371-9.
[] [PMID: 28495931]
Carmona-Rivera C, Zhao W, Yalavarthi S, Kaplan MJ. Neutrophil extracellular traps induce endothelial dysfunction in systemic lupus erythematosus through the activation of matrix metalloproteinase-2. Ann Rheum Dis 2015; 74(7): 1417-24.
[] [PMID: 24570026]
Grayson PC, Kaplan MJ. At the Bench: Neutrophil extracellular traps (NETs) highlight novel aspects of innate immune system involvement in autoimmune diseases. J Leukoc Biol 2016; 99(2): 253-64.
[] [PMID: 26432901]
Kougias P, Chai H, Lin PH, Yao Q, Lumsden AB, Chen C. Defensins and cathelicidins: neutrophil peptides with roles in inflammation, hyperlipidemia and atherosclerosis. J Cell Mol Med 2005; 9(1): 3-10.
[] [PMID: 15784160]
Wang J, Sjöberg S, Tang TT, et al. Cathepsin G activity lowers plasma LDL and reduces atherosclerosis. Biochim Biophys Acta 2014; 1842(11): 2174-83.
[] [PMID: 25092171]
Qi H, Yang S, Zhang L. Neutrophil extracellular traps and endothelial dysfunction in atherosclerosis and thrombosis. Front Immunol 2017; 8: 2017.00928/full.
[] [PMID: 28824648]
Knight JS, Luo W, O’Dell AA, et al. Peptidylarginine deiminase inhibition reduces vascular damage and modulates innate immune responses in murine models of atherosclerosis. Circ Res 2014; 114(6): 947-56.
[] [PMID: 24425713]
Smith CK, Vivekanandan-Giri A, Tang C, et al. Neutrophil extracellular trap-derived enzymes oxidize high-density lipoprotein: an additional proatherogenic mechanism in systemic lupus erythematosus. Arthritis Rheumatol 2014; 66(9): 2532-44.
[] [PMID: 24838349]
de Boer OJ, Li X, Teeling P, et al. Neutrophils, neutrophil extracellular traps and interleukin-17 associate with the organisation of thrombi in acute myocardial infarction. Thromb Haemost 2013; 109(2): 290-7.
[] [PMID: 23238559]
Maugeri N, Campana L, Gavina M, et al. Activated platelets present high mobility group box 1 to neutrophils, inducing autophagy and promoting the extrusion of neutrophil extracellular traps. J Thromb Haemost 2014; 12(12): 2074-88.
[] [PMID: 25163512]
Darbousset R, Thomas GM, Mezouar S, et al. Tissue factor-positive neutrophils bind to injured endothelial wall and initiate thrombus formation. Blood 2012; 120(10): 2133-43.
[] [PMID: 22837532]
Stakos DA, Kambas K, Konstantinidis T, et al. Expression of functional tissue factor by neutrophil extracellular traps in culprit artery of acute myocardial infarction. Eur Heart J 2015; 36(22): 1405-14.
[] [PMID: 25660055]
Fuchs TA, Brill A, Duerschmied D, et al. Extracellular DNA traps promote thrombosis. Proc Natl Acad Sci USA 2010; 107(36): 15880-5.
[] [PMID: 20798043]
Kambas K, Mitroulis I, Apostolidou E, et al. Autophagy mediates the delivery of thrombogenic tissue factor to neutrophil extracellular traps in human sepsis. PLoS One 2012; 7(9): e45427.
[] [PMID: 23029002]
Massberg S, Grahl L, von Bruehl ML, et al. Reciprocal coupling of coagulation and innate immunity via neutrophil serine proteases. Nat Med 2010; 16(8): 887-96.
[] [PMID: 20676107]
von Brühl ML, Stark K, Steinhart A, et al. Monocytes, neutrophils, and platelets cooperate to initiate and propagate venous thrombosis in mice in vivo. J Exp Med 2012; 209(4): 819-35.
[] [PMID: 22451716]
Gould TJ, Vu TT, Swystun LL, et al. Neutrophil extracellular traps promote thrombin generation through platelet-dependent and platelet-independent mechanisms. Arterioscler Thromb Vasc Biol 2014; 34(9): 1977-84.
[] [PMID: 25012129]
Shahidi M. Thrombosis and von Willebrand factor. Adv Exp Med Biol 2017; 906: 285-306.
[] [PMID: 27628010]
Fuchs TA, Brill A, Wagner DD. Neutrophil extracellular trap (NET) impact on deep vein thrombosis. Arterioscler Thromb Vasc Biol 2012; 32(8): 1777-83.
[] [PMID: 22652600]
Döring Y, Soehnlein O, Weber C. Neutrophil extracellular traps in atherosclerosis and atherothrombosis. Circ Res 2017; 120(4): 736-43.
[] [PMID: 28209798]
Noubouossie DF, Whelihan MF, Yu YB, et al. In vitro activation of coagulation by human neutrophil DNA and histone proteins but not neutrophil extracellular traps. Blood 2017; 129(8): 1021-9.
[] [PMID: 27919911]
Konig MF, Andrade F. A critical reappraisal of neutrophil extracellular traps and netosis mimics based on differential requirements for protein citrullination. Front Immunol 2016; 7: 461.
[] [PMID: 27867381]
Li H, Pan P, Su X, et al. Neutrophil extracellular traps are pathogenic in ventilator-induced lung injury and partially dependent on TLR4. BioMed Res Int 2017; 2017: bmri/2017/8272504/.
[] [PMID: 29387725]
Nakazawa D, Kumar SV, Marschner J, et al. Histones and neutrophil extracellular traps enhance tubular necrosis and remote organ injury in ischemic AKI. J Am Soc Nephrol 2017; 28(6): 1753-68.
[] [PMID: 28073931]
Agraz-Cibrián JM, Delgado-Rizo V, Segura-Ortega JE, et al. Impaired neutrophil extracellular traps and inflammatory responses in the peritoneal fluid of patients with liver cirrhosis. Scand J Immunol 2018; 88(5):
[] [PMID: 30226638]
Gottlieb Y, Elhasid R, Berger-Achituv S, Brazowski E, Yerushalmy-Feler A, Cohen S. Neutrophil extracellular traps in pediatric inflammatory bowel disease. Pathol Int 2018; 68(9): 517-23.
[] [PMID: 30133056]
Kim TY, Gu JY, Jung HS, Koh Y, Kim I, Kim HK. Elevated extracellular trap formation and contact system activation in acute leukemia. J Thromb Thrombolysis 2018; 46(3): 379-85.
[] [PMID: 30099724]
Lee KH, Cavanaugh L, Leung H, et al. Quantification of NETs-associated markers by flow cytometry and serum assays in patients with thrombosis and sepsis. Int J Lab Hematol 2018; 40(4): 392-9.
[] [PMID: 29520957]
Raup-Konsavage WM, Wang Y, Wang WW, Feliers D, Ruan H, Reeves WB. Neutrophil peptidyl arginine deiminase-4 has a pivotal role in ischemia/reperfusion-induced acute kidney injury. Kidney Int 2018; 93(2): 365-74.
[] [PMID: 29061334]
Guo R, Tu Y, Xie S, et al. A role for receptor-interacting protein kinase-1 in neutrophil extracellular trap formation in patients with systemic lupus erythematosus: a preliminary study. Cell Physiol Biochem 2018; 45(6): 2317-28.
[] [PMID: 29550813]
Mauracher LM, Posch F, Martinod K, et al. Citrullinated histone H3, a biomarker of neutrophil extracellular trap formation, predicts the risk of venous thromboembolism in cancer patients. J Thromb Haemost 2018; 16(3): 508-18.
[] [PMID: 29325226]
Thålin C, Lundström S, Seignez C, et al. Citrullinated histone H3 as a novel prognostic blood marker in patients with advanced cancer. PLoS One 2018; 13(1): e0191231.
[] [PMID: 29324871]

Rights & Permissions Print Export Cite as
© 2022 Bentham Science Publishers | Privacy Policy