Circulating histone H3 levels are increased in septic mice in a neutrophil-dependent manner: preclinical evaluation of a novel sandwich ELISA for histone H3

Journal of Intensive Care

Mayumi Nakahara¹  Hitoshi Imaizumi²  Hiroyasu Ishikura³  Chinatsu Kamikokuryo⁴  Yasuyuki Kakihana⁴  Yoshiki Masuda⁵  Takashi Ito⁶  Ikuro Maruyama⁶  Sachie Ono⁷  Shingo Yamada⁷ 

[1] Department of Anesthesiology and Critical Care Medicine, Kagoshima University Graduate School of Medical and Dental Sciences;Department of Anesthesiology and Intensive Care Medicine, Tokyo Medical University;Department of Emergency and Critical Care Medicine, Faculty of Medicine, Fukuoka University;Department of Emergency and Intensive Care Medicine, Kagoshima University Graduate School of Medical and Dental Sciences;Department of Intensive Care Medicine, Sapporo Medical University School of Medicine;Department of Systems Biology in Thromboregulation, Kagoshima University Graduate School of Medical and Dental Sciences;R&D Center, Shino-Test Corporation;

关键词: Histone;    Sepsis;    Neutrophil;    ELISA;   

DOI  :  10.1186/s40560-018-0348-y

来源: DOAJ

【 摘 要 】

Abstract Background Nuclear histone proteins are released into the extracellular space during sepsis and act as major mediators of death. However, circulating histone levels have not been precisely quantified. Methods We developed a novel enzyme-linked immunosorbent assay (ELISA) for detection of circulating histone H3 levels and evaluated its performance. Using the ELISA, we measured plasma histone H3 levels in C57BL/6 J mice subjected to cecal ligation and puncture (CLP)-induced sepsis. Results The newly developed ELISA enabled reproducible measurement of histone H3 levels with a working range up to 250 ng/mL. Using the ELISA, we found that plasma histone H3 levels were elevated in septic mice compared with sham-operated mice (p < 0.01). The elevation of histone H3 levels was abrogated when neutrophils were depleted (p < 0.01). Conclusions Our novel ELISA provides reproducible measurements of histone H3 levels. Circulating histone H3 levels are increased in septic mice in a neutrophil-dependent manner. Further studies are needed to evaluate the clinical utility of histone H3 levels in patients with sepsis.

【 授权许可】

Unknown