Elucidation of idiopathic pneumonia syndrome: Angiotensin 2 activates alveolar macrophages

2022 Fiscal Year Final Research Report

• Project/Area Number: 21K16251
• 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): 2021-04-01 – 2023-03-31
• Keywords: 特発性肺炎症候群 / 肺胞マクロファージ / インフラマソーム

Outline of Final Research Achievements

Expression of the inflammasome NLRP3 and of caspase-1 and IL-1β, whose activation is regulated by NLRP3, was comparable to wild-type in post-transplantation lungs of liver-specific angiotensinogen knockout mice. Therefore, no correlation was found between the renin-angiotensin system and the inflammasome expression in this experimental model.

When NR8383 was stimulated with bleomycin in vitro, angiotensinogen expression was enhanced. This upregulation of angiotensinogen was not affected by angiotensin II or angiotensin receptor inhibitors. On the other hand, the addition of angiotensinogen further enhanced the induction of angiotensinogen expression by bleomycin.

Free Research Field

血液内科学

Academic Significance and Societal Importance of the Research Achievements

肺全体でのアンジオテンシノゲンの発現は肝臓での発現がノックアウトしていると亢進し、一方で肺胞マクロファージではアンジオテンシノゲンによるポジティブフィードバック反応を認めた。この結果より、肺胞マクロファージ以外の細胞によるネガティブフィードバック機構の存在と、肺胞マクロファージにおけるアンジオテンシノゲン受容体の存在が示唆された。