Origin of Circulating Free DNA in Sepsis: Analysis of the CLP Mouse Model.
Recently, 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.
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.
Shigeto
S
Hamaguchi
International Research Center for Infectious Diseases, Research Institute for Microbial Diseases, Osaka University, Osaka 565-0871, Japan.
Yukihiro
Y
Akeda
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.
Norihisa
N
Yamamoto
Division of Infection Control and Prevention, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan.
Masafumi
M
Seki
Department of Clinical Epidemiology and Biostatistics, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan.
Kouji
K
Yamamoto
International Research Center for Infectious Diseases, Research Institute for Microbial Diseases, Osaka University, Osaka 565-0871, Japan ; Infectious Disease Surveillance Center, National Institute of Infectious Diseases, Tokyo 162-8640, Japan.
Kazunori
K
Oishi
Division of Infection Control and Prevention, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan.
Kazunori
K
Tomono
D000818:Animals; D004247:DNA / Q000097:blood*; D004195:Disease Models, Animal; D008026:Ligation; D051379:Mice; D008810:Mice, Inbred C57BL; D009504:Neutrophils / Q000166:cytology*; D018805:Sepsis / Q000097:blood* / Q000235:genetics*
D004247:DNA