Extracellular histones in tissue injury and inflammation

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 o...

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Bibliographic Details
Published in:Journal of molecular medicine (Berlin, Germany) Germany), 2014-05, Vol.92 (5), p.465-472
Main Authors: Allam, Ramanjaneyulu, Kumar, Santhosh V. R., Darisipudi, Murthy N., Anders, Hans-Joachim
Format: Article
Language:English
Subjects:
Acute Kidney Injury - immunology
Animals
Autoimmune Diseases - immunology
Biomedical and Life Sciences
Biomedicine
Histones - analysis
Histones - immunology
Human Genetics
Humans
Inflammation - immunology
Internal Medicine
Ischemia - immunology
Lung Injury - immunology
Molecular Medicine
Protein Conformation
Review
Sepsis - immunology
Thrombosis - immunology
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Summary: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.
ISSN:0946-2716
1432-1440
DOI:10.1007/s00109-014-1148-z