| Project/Area Number |
24659797
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Multi-year Fund |
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| Research Field |
Emergency medicine
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| Research Institution | Kagoshima University |
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Principal Investigator |
ITO Takashi 鹿児島大学, 大学院・医歯学総合研究科, 特任講師 (20381171)
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| Co-Investigator(Kenkyū-buntansha) |
MARUYAMA Ikuro 鹿児島大学, 大学院・医歯学総合研究科, 特任教授 (20082282)
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| Co-Investigator(Renkei-kenkyūsha) |
KAWAHARA Ko-ichi 大阪工業大学, 工学部生命工学科, 特任教授 (10381170)
NAKAHARA Mayumi 鹿児島大学医学部, 歯学部附属病院, 助教 (90707514)
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| Research Collaborator |
YAMADA Shingo 株式会社, シノテスト
NAGASATO Tomoka 藤森工業株式会社
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| Project Period (FY) |
2012
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| Project Status |
Completed (Fiscal Year 2012)
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| Budget Amount *help |
¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2012: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
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| Keywords | 集中治療医学 / 敗血症 / DIC / 炎症 / 血栓 / DAMPs |
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| Research Abstract |
We developed a sandwich ELISA to quantify serum or plasma histone H3 levels. The working range of this ELISA was 10-1000μg/L. Histone H3 was not detectable in plasma of healthy volunteers, but significant levels were observed in patients with sepsis and DIC. These levels were higher in non-survivors compared to survivors. Extracellular histones triggered platelet aggregation, leading to thrombotic occlusion of pulmonary capillaries and subsequent right-sided heart failure in mice. These mice displayed signs of DIC, including thrombocytopenia, prolonged prothrombin time, decreased fibrinogen, fibrin deposition in capillaries, and bleeding symptoms. These findings indicate that histones are released into the extracellular space during sepsis and act as a trigger for fatal thrombotic disorders.
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