The Novel Hemostatic and Tissue Protective Treatment Elucidating the Pathophysiology of Blast Lung Injury

2015 Fiscal Year Final Research Report

• Project/Area Number: 25462843
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Emergency medicine
• Research Institution: National Defense Medical College
• Principal Investigator: HAGISAWA KOHSUKE 防衛医科大学校(医学教育部医学科進学課程及び専門課程、動物実験施設、共同利用研究, 医学教育部医学科専門課程, 助教 (50539244)
• Co-Investigator(Kenkyū-buntansha): KINOSHITA Manabu 防衛医科大学校, 医学教育部医学科専門課程, 准教授 (70531391) ; SATOH Shunichi 防衛医科大学校, 防衛医学研究センター, 准教授 (90502906) ; SUZUKI Hidenori 日本医科大学, 医学部, 准教授 (30158977)
• Co-Investigator(Renkei-kenkyūsha): TAKEOKA Shinji 早稲田大学, 理工学術院, 教授 (20222094) ; SAITOH Daizoh 防衛医科大学校, 防衛医学研究センター, 教授 (90531632) ; HANDA Makoto 慶應義塾大学, 医学部, 教授 (40129614)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: Blast Lung Injury / 止血凝固作用 / アデノシン作用 / レーザー誘起衝撃波 / ドラッグデリバリシステム

Outline of Final Research Achievements

Fibrinogen gamma-chain (HHLGGAKQAGDV, H12)-coated, adenosine diphosphate-encapsulated liposomes [H12-(ADP)-liposomes] can accumulate at bleeding sites where they release ADP that is rapidly metabolized to adenosine, which has tissue-protective effects.
We investigated the efficacy of H12-(ADP)-liposomes to treat blast lung injury, with a focus on adenosine signaling. Pretreatment as well as post-treatment with H12-(ADP)-liposomes significantly increased mouse survivals and mitigated pulmonary tissue damage/hemorrhage and neutrophil accumulation after LISW exposure. Pretreatment with H12-(ADP)-liposomes reduced albumin and macrophage inflammatory protein-2 levels in bronchoalveolar lavage fluid. Although H12-(ADP)-liposome pretreatment did not affect blood coagulation activity in the injured mice, its beneficial effect on blast lung injury were significantly abrogated by adenosine receptor A2A or A2B antagonism, suggesting that adenosine signaling improved lung injury.

Free Research Field

生理学、循環器内科学