About: Extracellular histones trigger disseminated intravascular coagulation by lytic cell death

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type	Academic Article research paper schema:ScholarlyArticle
isDefinedBy	Covid-on-the-Web dataset
has title	Extracellular histones trigger disseminated intravascular coagulation by lytic cell death
Creator	Zhang, Yan Cui, Jian Li, Zhenyu Li, Lan Kirchhofer, Daniel Pandeya, Ankit Smyth, Susan Wei, Yinan Wood, Jeremy Wu, Congqing Zhang, Guoying
Source	BioRxiv
abstract	Histones are cationic nuclear proteins that are essential for the structure and functions of eukaryotic chromatin. However, extracellular histones trigger inflammatory responses and contribute to death in sepsis by unknown mechanisms. We recently reported that inflammasome activation and pyroptosis trigger coagulation activation through a tissue factor (TF)-dependent mechanism. Here, we show that histones trigger coagulation activation in vivo as evidenced by coagulation parameters and fibrin deposition in tissues. However, histone-induced coagulopathy was neither dependent on caspase 1/11 and gasdermin D (GSDMD), nor on TLR2 and TLR4, as deficiency of these genes in mice did not protect against histone-induced coagulopathy. Incubation of histones with macrophages induced lytic cell death and phosphatidylserine (PS) exposure, which is required for TF activity, a key initiator of coagulation. Neutralization of TF diminished histone-induced coagulation. Our findings reveal lytic cell death as a novel mechanism of histone-induce coagulation activation and thrombosis. Key Points Histones trigger DIC in a tissue factor dependent mechanism Histones induce tissue factor activation through lytic cell death
has issue date	2020-06-12(xsd:dateTime)
bibo:doi	10.1101/2020.06.11.144683
has license	biorxiv
sha1sum (hex)	728b43cc94e46f9b0a4a1643220e6ca28c9a5217
schema:url	https://doi.org/10.1101/2020.06.11.144683
resource representing a document's title	Extracellular histones trigger disseminated intravascular coagulation by lytic cell death
schema:publication	bioRxiv
resource representing a document's body	covid:728b43cc94e46f9b0a4a1643220e6ca28c9a5217#body_text
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