IMR Press / FBL / Volume 20 / Issue 8 / DOI: 10.2741/4370

Frontiers in Bioscience-Landmark (FBL) is published by IMR Press from Volume 26 Issue 5 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on imrpress.com as a courtesy and upon agreement with Frontiers in Bioscience.

Open Access Article
Heparin defends against the toxicity of circulating histones in sepsis
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1 The Key Laboratory of Pediatric Hematology and Oncology Ministry of Health, Institute for Pediatric Translational Medicine, Shanghai Children’s Medical Center, Shanghai Jiaotong University School of Medicine, Shanghai, China
2 Department of Critical Care Medicine, Shanghai Children’s Medical Center, Shanghai Jiaotong University School of Medicine, Shanghai, China
3 Department of infectious diseases, Shanghai Children’s Medical Center, Shanghai Jiaotong University School of Medicine, Shanghai, China
4 Department of Pediatric, Hunan Children’s Hospital, China
Academic Editor:Fei He
Front. Biosci. (Landmark Ed) 2015, 20(8), 1259–1270; https://doi.org/10.2741/4370
Published: 1 June 2015
(This article belongs to the Special Issue Cellular immunology and stem cell biology)
Abstract

Although circulating histones were demonstrated as major mediators of death in septic mice models, their roles in septic patients are not clarified. The present study sought to evaluate the clinical relevance of the circulating histone levels in septic children, and the antagonizing effects of heparin on circulating histones. Histone levels in the plasma of septic children were significantly higher than healthy controls, and positively correlated with disease severity. Histone treatment could activate NF-κB pathway of the endothelial cells and induce the secretion of large amount of cytokines that further amplify inflammation, subsequently leading to organ damage. Co-injection of low dose heparin with lethal dose histones could protect mouse from organ damage and death by antagonizing circulating histones, and similar effects were also observed in other septic models. Collectively, these findings indicated that circulating histones might serve as key factors in the pathogenesis of sepsis and their levels in plasma might be a marker for disease progression and prognosis. Furthermore, low dose heparin might be an effective therapy to hamper sepsis progression and reduce the mortality.

Keywords
Heparin
Circulating histones
Sepsis
Non-anticoagulant
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