• Shigeto Hamaguchi, Yukihiro Akeda, Norihisa Yamamoto, Masafumi Seki, Kouji Yamamoto, Kazunori Oishi, and Kazunori Tomono.
• Division of Infection Control and Prevention, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan ; International Research Center for Infectious Diseases, Research Institute for Microbial Diseases, Osaka University, Osaka 565-0871, Japan.
• Mediators Inflamm. 2015 Jan 1; 2015: 614518.

AbstractRecently, it has been reported that circulating free DNA (cf-DNA) in the blood is increased in various infectious diseases, including sepsis. Moreover, a relationship between cf-DNA and neutrophil extracellular traps (NETs) has been suggested. However, it is still unclear what the source and physiological role of cf-DNA in sepsis are. In this study, we examined the source of cf-DNA by detecting citrullinated histone H3, a characteristic feature of NET formation, in cecal ligation and puncture- (CLP-)operated mice. In addition, neutrophil depletion using anti-Ly6G antibodies was performed to assess the association between neutrophils and cf-DNA. Increased cf-DNA levels were observed only in CLP mice and not in the control groups; the qPCR findings revealed that the cf-DNA was mainly host-derived, even in bacteremic conditions. Citrullinated histone H3 was not increased in the neutrophils upon CLP, and the depletion of neutrophils showed limited effects on decreasing the amount of cf-DNA. Taken together, these results suggested that elevated cf-DNA levels during early-phase sepsis may represent a candidate biomarker for the severity of sepsis and that, contrary to previous findings, cf-DNA is not derived from neutrophils or NETs.

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