title: Heparin defends against the toxicity of circulating histones in sepsis.
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.
authors.forename: Feifei
authors.initials: F
authors.lastname: Wang
authors.forename: Naipu
authors.initials: N
authors.lastname: Zhang
authors.forename: Biru
authors.initials: B
authors.lastname: Li
authors.forename: Lanbo
authors.initials: L
authors.lastname: Liu
authors.forename: Lei
authors.initials: L
authors.lastname: Ding
authors.affiliation: Department of Clinical Biochemistry, Chinese PLA General Hospital, No.28, Fuxing Road, Beijing, China, 100853.
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.forename: Yimin
authors.initials: Y
authors.lastname: Zhu
authors.forename: Xi
authors.initials: X
authors.lastname: Mo
authors.affiliation: Department of infectious diseases, Shanghai Children's Medical Center, 1678 Dongfang Rd., Shanghai, 200127, China, caoqing9@yeah.net.
authors.forename: Qing
authors.initials: Q
authors.lastname: Cao
mesh_terms: D000818:Animals; D002675:Child, Preschool; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D006493:Heparin / Q000627:therapeutic use*; D006657:Histones / Q000097:blood* / Q000633:toxicity; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D007223:Infant; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D020011:Protective Agents / Q000627:therapeutic use*; D018805:Sepsis / Q000097:blood*
chemical_list: D006657:Histones; D020011:Protective Agents; D006493:Heparin