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Extracellular histones in tissue injury and inflammation.

Authors
  • Allam, Ramanjaneyulu
  • Kumar, Santhosh V R
  • Darisipudi, Murthy N
  • Anders, Hans-Joachim
Type
Published Article
Journal
Journal of Molecular Medicine
Publisher
Springer-Verlag
Publication Date
May 01, 2014
Volume
92
Issue
5
Pages
465–472
Identifiers
DOI: 10.1007/s00109-014-1148-z
PMID: 24706102
Source
Medline
License
Unknown

Abstract

Neutrophil NETosis is an important element of host defense as it catapults chromatin out of the cell to trap bacteria, which then are killed, e.g., by the chromatin's histone component. Also, during sterile inflammation TNF-alpha and other mediators trigger NETosis, which elicits cytotoxic effects on host cells. The same mechanism should apply to other forms of regulated necrosis including pyroptosis, necroptosis, ferroptosis, and cyclophilin D-mediated regulated necrosis. Beyond these toxic effects, extracellular histones also trigger thrombus formation and innate immunity by activating Toll-like receptors and the NLRP3 inflammasome. Thereby, extracellular histones contribute to the microvascular complications of sepsis, major trauma, small vessel vasculitis as well as acute liver, kidney, brain, and lung injury. Finally, histones prevent the degradation of extracellular DNA, which promotes autoimmunization, anti-nuclear antibody formation, and autoimmunity in susceptible individuals. Here, we review the current evidence on the pathogenic role of extracellular histones in disease and discuss how to target extracellular histones to improve disease outcomes.

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