Elucidation of post-transplant idiopathic pneumonia syndrome: is angiotensinogen a predictor and prophylaxis?

2020 Fiscal Year Final Research Report

• Project/Area Number: 19K17872
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 54010:Hematology and medical oncology-related
• Research Institution: Tokai University
• Principal Investigator: Hara Ryujiro 東海大学, 医学部, 助教 (90750026)
• Project Period (FY): 2019-04-01 – 2021-03-31
• Keywords: アンジオテンシノゲン / 造血幹細胞移植 / ブレオマイシン

Outline of Final Research Achievements

Infiltration of CD3-positive T cells was observed in the lungs after bone marrow transplantation into wild-type mice. Expression of angiotensinogen in the lung was lower than that of controls. Two weeks after transplantation into a liver-specific angiotensinogen knockout mice in which the blood concentration of angiotensinogen decreases, lung function tests and inflammatory cytokine expression were exacerbated in the knockout mice. The survival rate was reduced in the knockout mice. Both wild-type and knockout mice had increased production of angiotensinogen in alveolar macrophages after transplantation. Expression of the HMGB1-RAGE system in the lung was comparable in both wild-type and liver-specific angiotensinogen knockout mice.

Free Research Field

血液内科学

Academic Significance and Societal Importance of the Research Achievements

血圧調節に関わるアンジオテンシノゲンによる様々な病態増悪機序が知られているが、本研究では血中のアンジオテンシノゲンが低い肝臓特異的アンジオテンシノゲンノックアウトマウスで、肺でのアンジオテンシノゲンの発現が逆に亢進し、移植後肺障害やブレオマイシン肺障害が増悪していた。このことは、各臓器でのアンジオテンシノゲンの発現量やその臓器障害は血中のアンジオテンシノゲン濃度測定では予測できない事を示している。