Neutrophil extracellular traps — the dark side of neutrophils
Open Access
- 2 May 2016
- journal article
- review article
- Published by American Society for Clinical Investigation in JCI Insight
- Vol. 126 (5), 1612-1620
- https://doi.org/10.1172/jci84538
Abstract
Neutrophil extracellular traps (NETs) were discovered as extracellular strands of decondensed DNA in complex with histones and granule proteins, which were expelled from dying neutrophils to ensnare and kill microbes. NETs are formed during infection in vivo by mechanisms different from those originally described in vitro. Citrullination of histones by peptidyl arginine deiminase 4 (PAD4) is central for NET formation in vivo. NETs may spur formation of autoantibodies and may also serve as scaffolds for thrombosis, thereby providing a link among infection, autoimmunity, and thrombosis. In this review, we present the mechanisms by which NETs are formed and discuss the physiological and pathophysiological consequences of NET formation. We conclude that NETs may be of more importance in autoimmunity and thrombosis than in innate immune defense.Keywords
This publication has 113 references indexed in Scilit:
- Neutrophil histone modification by peptidylarginine deiminase 4 is critical for deep vein thrombosis in miceProceedings of the National Academy of Sciences of the United States of America, 2013
- Statins Enhance Formation of Phagocyte Extracellular TrapsCell Host & Microbe, 2010
- Neutrophil elastase and myeloperoxidase regulate the formation of neutrophil extracellular trapsThe Journal of cell biology, 2010
- PAD4 is essential for antibacterial innate immunity mediated by neutrophil extracellular trapsThe Journal of Experimental Medicine, 2010
- Extracellular DNA traps promote thrombosisProceedings of the National Academy of Sciences of the United States of America, 2010
- Impairment of neutrophil extracellular trap degradation is associated with lupus nephritisProceedings of the National Academy of Sciences of the United States of America, 2010
- Netting neutrophils in autoimmune small-vessel vasculitisNature Medicine, 2009
- Histone hypercitrullination mediates chromatin decondensation and neutrophil extracellular trap formationThe Journal of cell biology, 2009
- Novel cell death program leads to neutrophil extracellular trapsThe Journal of cell biology, 2007
- Loss-of-function mutations in cathepsin C in two families with Papillon-Lefèvre syndrome are associated with deficiency of serine proteinases in PMNsHuman Mutation, 2004