ArticleInternational journal of molecular sciences2022
Extracellular Histones Trigger Disseminated Intravascular Coagulation by Lytic Cell Death.
Article in International journal of molecular sciences, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 16 citations in OpenAlex.
- Emerging biomodels to understand the pathophysiology of sepsis and evaluate new therapeutic strategies targeting extracellular histones.Materials today. Bio · 2026Review
- Disseminated intravascular coagulation.Journal of intensive care · 2025Review
- Extracellular histones: a unifying mechanism driving platelet-dependent extracellular vesicle release and thrombus formation in COVID-19.Journal of thrombosis and haemostasis : JTH · 2024Article
- Trauma-associated extracellular histones mediate inflammation via a MYD88-IRAK1-ERK signaling axis and induce lytic cell death in human adipocytes.Cell death & disease · 2024Article
- Emerging therapeutic strategies targeting extracellular histones for critical and inflammatory diseases: an updated narrative review.Frontiers in immunology · 2024Review
- Gasdermin D: A Potential New Auxiliary Pan-Biomarker for the Detection and Diagnosis of Diseases.Biomolecules · 2023Review
- Targeting circulating high mobility group box-1 and histones by extracorporeal blood purification as an immunomodulation strategy against critical illnesses.Critical care (London, England) · 2023Review
- Novel mechanisms of thrombo-inflammation during infection: spotlight on neutrophil extracellular trap-mediated platelet activation.Research and practice in thrombosis and haemostasis · 2023Article
- Pyroptotic cell death in SARS-CoV-2 infection: revealing its roles during the immunopathogenesis of COVID-19.International journal of biological sciences · 2022Review
- Review
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 2 countries.
Funding
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 surface receptor TLR2- and TLR4-mediated host immune response, as the deficiency of these genes in mice did not protect against histone-induced coagulopathy. The incubation of histones with macrophages induced lytic cell death and phosphatidylserine (PS) exposure, which is required for TF activity, a key initiator of coagulation. The neutralization of TF diminished the histone-induced coagulation. Our findings revealed lytic cell death as a novel mechanism of histone-induced coagulation activation and thrombosis.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.