Extracellular histones stimulate endothelial cells to release unusually-large von Willebrand factor multimer: mechanistic insight into the pathogenesis of lethal coagulopathy

2014 Fiscal Year Final Research Report

• Project/Area Number: 26670789
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Emergency medicine
• Research Institution: Kagoshima University
• Principal Investigator: ITO Takashi 鹿児島大学, 医歯(薬)学総合研究科, 講師 (20381171)
• 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)
• 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)
• Research Collaborator: NAGASATO Tomoka 藤森工業株式会社 ; YAMADA Shingo 株式会社シノテスト
• Project Period (FY): 2014-04-01 – 2015-03-31
• 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

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).

Free Research Field

血栓症