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

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.

• Authors: Takashi Ito, Mayumi Nakahara, Yoshiki Masuda, Sachie Ono, Shingo Yamada, Hiroyasu Ishikura, Hitoshi Imaizumi, Chinatsu Kamikokuryo, Yasuyuki Kakihana, Ikuro Maruyama
• Journal: Journal of intensive care (J Intensive Care) Vol. 6 Pg. 79 ( 2018) ISSN: 2052-0492 [Print] England
• PMID: 30505450 (Publication Type: Journal Article)