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Review
. 2016 May 2;126(5):1612-20.
doi: 10.1172/JCI84538. Epub 2016 May 2.

Neutrophil extracellular traps - the dark side of neutrophils

Ole E Sørensen, Niels Borregaard
Review

Neutrophil extracellular traps - the dark side of neutrophils

Ole E Sørensen et al. J Clin Invest. .

Abstract (V体育ios版)

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 VSports手机版. 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. .

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Figures

Figure 1
Figure 1. NET formation.
In activated neutrophils PAD4 citrullinates certain histone arginines, and the tight electrostatic binding between histones and DNA in nucleosomes is weakened. Nuclear and granule membranes are dissolved. Decondensed DNA with citrullinated histones and granule proteins meet and are expelled from the neutrophil as NETs that may ensnare and possibly kill microbes. The surface membrane reseals and leaves a viable anuclear neutrophil behind. Cit, citrulline.
Figure 2
Figure 2. NET-associated histone modifications.
NETs contain antigens, some of which are modified histones that act as neoantigens to induce formation of autoantibodies that induce or accelerate vasculitis, rheumatoid arthritis, and thrombus formation.
See this image and copyright information in PMC

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