Journal
JOURNAL OF INTENSIVE CARE
Volume 6, Issue -, Pages -Publisher
BMC
DOI: 10.1186/s40560-018-0348-y
Keywords
Histone; Sepsis; Neutrophil; ELISA
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Funding
- Japan Society for the Promotion of Science [24659797, 15H05684]
- Grants-in-Aid for Scientific Research [24659797, 15H05684] Funding Source: KAKEN
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BackgroundNuclear 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.MethodsWe 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/6J mice subjected to cecal ligation and puncture (CLP)-induced sepsis.ResultsThe newly developed ELISA enabled reproducible measurement of histone H3 levels with a working range up to 250ng/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).ConclusionsOur 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.
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