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 physiol...
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| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2015-01-01
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| Series: | Mediators of Inflammation |
| Online Access: | http://dx.doi.org/10.1155/2015/614518 |
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| _version_ | 1832556967982268416 |
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| author | Shigeto Hamaguchi Yukihiro Akeda Norihisa Yamamoto Masafumi Seki Kouji Yamamoto Kazunori Oishi Kazunori Tomono |
| author_facet | Shigeto Hamaguchi Yukihiro Akeda Norihisa Yamamoto Masafumi Seki Kouji Yamamoto Kazunori Oishi Kazunori Tomono |
| author_sort | Shigeto Hamaguchi |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-a07fdbba7fdd45f6b49c32518adf1728 |
| institution | Kabale University |
| issn | 0962-9351 1466-1861 |
| language | English |
| publishDate | 2015-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Mediators of Inflammation |
| spelling | doaj-art-a07fdbba7fdd45f6b49c32518adf17282025-02-03T05:44:04ZengWileyMediators of Inflammation0962-93511466-18612015-01-01201510.1155/2015/614518614518Origin of Circulating Free DNA in Sepsis: Analysis of the CLP Mouse ModelShigeto Hamaguchi0Yukihiro Akeda1Norihisa Yamamoto2Masafumi Seki3Kouji Yamamoto4Kazunori Oishi5Kazunori Tomono6Division of Infection Control and Prevention, Osaka University Graduate School of Medicine, Osaka 565-0871, JapanInternational Research Center for Infectious Diseases, Research Institute for Microbial Diseases, Osaka University, Osaka 565-0871, JapanDivision of Infection Control and Prevention, Osaka University Graduate School of Medicine, Osaka 565-0871, JapanDivision of Infection Control and Prevention, Osaka University Graduate School of Medicine, Osaka 565-0871, JapanDepartment of Clinical Epidemiology and Biostatistics, Osaka University Graduate School of Medicine, Osaka 565-0871, JapanInternational Research Center for Infectious Diseases, Research Institute for Microbial Diseases, Osaka University, Osaka 565-0871, JapanDivision of Infection Control and Prevention, Osaka University Graduate School of Medicine, Osaka 565-0871, JapanRecently, 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.http://dx.doi.org/10.1155/2015/614518 |
| spellingShingle | Shigeto Hamaguchi Yukihiro Akeda Norihisa Yamamoto Masafumi Seki Kouji Yamamoto Kazunori Oishi Kazunori Tomono Origin of Circulating Free DNA in Sepsis: Analysis of the CLP Mouse Model Mediators of Inflammation |
| title | Origin of Circulating Free DNA in Sepsis: Analysis of the CLP Mouse Model |
| title_full | Origin of Circulating Free DNA in Sepsis: Analysis of the CLP Mouse Model |
| title_fullStr | Origin of Circulating Free DNA in Sepsis: Analysis of the CLP Mouse Model |
| title_full_unstemmed | Origin of Circulating Free DNA in Sepsis: Analysis of the CLP Mouse Model |
| title_short | Origin of Circulating Free DNA in Sepsis: Analysis of the CLP Mouse Model |
| title_sort | origin of circulating free dna in sepsis analysis of the clp mouse model |
| url | http://dx.doi.org/10.1155/2015/614518 |
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