Elucidation of an inhibitory mechanism of septic immunothrombosis by novel plasma factor:HRG

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K15580
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: General pharmacology
• Research Institution: Okayama University
• Principal Investigator: Wake Hidenori 岡山大学, 医歯薬学総合研究科, 講師 (60570520)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: HRG / 敗血症 / 免疫血栓形成

Outline of Final Research Achievements

Histidine-rich glycoprotein (HRG) is a plasma glycoprotein. Plasma HRG levels decreased in septic condition and HRG supplementary therapy improves lethality in sepsis. We elucidated that HRG modulates a dysregulated immunothrombus formation by suppression of aggregation of neutrophils, platelets and erythrocytes, and adhesion of these cells to endothelial cells because HRG detoxifies immunothrombosis-inducing factors (LPS, zinc, reactive oxygen species, polyphosphate). Additionally, we were successful in intravital visualization of these phenomena.

Free Research Field

血管・血液薬理学

Academic Significance and Societal Importance of the Research Achievements

HRGが敗血症病態を改善するより詳細な作用機序を明らかにすることにより、正しい敗血症の理解に寄与するとともに、新たな視点からの敗血症治療薬の開発に貢献する。また、今回構築した生体内イメージングの手法は、より正確な生体内血球細胞動態や血管状態を把握する上で役立ち、敗血症のみならず、他の病態への応用も可能である。