Extracellular histones stimulate endothelial cells to release unusually-large von Willebrand factor multimer: mechanistic insight into the pathogenesis of lethal coagulopathy
| Project/Area Number |
26670789
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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, 医歯(薬)学総合研究科, 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) |
MATSUMOTO Masanori 奈良県立医科大学, 教授 (60316081)
HAYAKAWA Masaki 奈良県立医科大学, 助教 (30516729)
NAKAHARA Mayumi 鹿児島大学, 大学院医歯学総合研究科, 特任助教 (90707514)
KAWAHARA Ko-ichi 大阪工業大学, 工学部生命工学科, 特任教授 (10381170)
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| Research Collaborator |
NAGASATO Tomoka 藤森工業株式会社
YAMADA Shingo 株式会社シノテスト
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| Project Period (FY) |
2014-04-01 – 2015-03-31
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| Project Status |
Completed (Fiscal Year 2014)
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| Budget Amount *help |
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2014: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
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| Keywords | 敗血症 / 血栓症 / ヒストン / 血管内皮細胞 / von Willebrand因子 / トロンボモジュリン / 細胞外ヒストン / 血栓性微小血管障害症 |
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| Outline of Final Research Achievements |
Extracellular histones stimulated endothelial cells to release von Willebrand factor (VWF). This resulted in massive thrombosis in glomeruli of histone-injected rats. Recombinant thrombomodulin bound to histones and inhibited histone-induced VWF-rich thrombus formation in rats. These findings suggest a novel role of extracellular histones in the pathogenesis of lethal coagulopathy, including thrombotic microangiopathy (TMA) and disseminated intravascular coagulation (DIC).
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Report
(2 results)
Research Products
(6 results)
