Extracellular Histones Trigger Disseminated Intravascular Coagulation by Lytic Cell Death.

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. We used a combination of various deficient mice to elucidate the molecular mechanism of histone-induced coagulation. We showed 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 intracellular inflammasome pathways involving caspase 1/11 and gasdermin D (GSDMD), nor on cell surfac

SUBMITTER: Zhang Y 

PROVIDER: S-EPMC9224270 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature