Therapeutic strategy targeting extracellular histones in sepsis-associated DIC

2017 Fiscal Year Final Research Report

• Project/Area Number: 15H05684
• Research Category: Grant-in-Aid for Young Scientists (A)
• Allocation Type: Single-year Grants
• Research Field: Emergency medicine
• Research Institution: Kagoshima University
• Principal Investigator: ITO Takashi 鹿児島大学, 医歯学総合研究科, 講師 (20381171)
• Co-Investigator(Renkei-kenkyūsha): MARUYAMA IKURO 鹿児島大学, 大学院医歯学総合研究科, 特任教授 (20082282) ; NAKAHARA MAYUMI 鹿児島大学, 医歯学域医学系, 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): 2015-04-01 – 2018-03-31
• Keywords: 敗血症 / 播種性血管内凝固症候群 / 細胞外ヒストン / トロンボモジュリン / コンドロイチン硫酸

Outline of Final Research Achievements

Recombinant thrombomodulin (rTM) inhibited histone-induced platelet aggregation and neutrophil extracellular trap (NET) formation in vitro. rTM also inhibited histone-induced NET formation in kidneys, and attenuated histone-induced renal dysfunction in rats. rTM with a chondroitin sulfate side chain (rTM type II) had higher affinity for histone H3 and H4 than the traditional rTM (Type I), and thus, inhibited histone-induced platelet aggregation and NET formation more efficiently than rTM type I. These findings suggest that rTM type II can be a promising therapeutic option for sepsis-associated disseminated intravascular coagulation. Further studies are needed to elucidate in vivo effects of rTM type II in septic conditions.

Free Research Field

救急・集中治療