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- Title
Extracellular histones in tissue injury and inflammation.
- Authors
Allam, Ramanjaneyulu; Kumar, Santhosh; Darisipudi, Murthy; Anders, Hans-Joachim
- 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.
- Subjects
HISTONES; TISSUE wounds; BACTERIAL chromatin; NATURAL immunity; TOLL-like receptors; NECROSIS; VASCULITIS
- Publication
Journal of Molecular Medicine, 2014, Vol 92, Issue 5, p465
- ISSN
0946-2716
- Publication type
Article
- DOI
10.1007/s00109-014-1148-z