Establishment of an Asthma-COPD Overlap (ACO) Mouse Model Using Papain

2023 Fiscal Year Final Research Report

• Project/Area Number: 18K15946
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 53030:Respiratory medicine-related
• Research Institution: The University of Tokyo
• Principal Investigator: Hiraishi Yoshihisa 東京大学, 医学部附属病院, 届出研究員 (90783514)
• Project Period (FY): 2018-04-01 – 2024-03-31
• Keywords: ACO / 喘息 / COPD

Outline of Final Research Achievements

We focused on papain, a cysteine protease from the plant papaya, as an animal model that conveniently reproduces the clinical features of ACO. We compared a pig pancreatic elastase (PPE)-induced COPD model and a PBS-treated group with a model in which papain was repeatedly administered. In the lung pathology of each group, emphysema formation was observed in the PPE and papain groups. Eosinophils in bronchoalveolar lavage fluid were significantly increased in the repeated papain-treated mice compared to the other groups, and in the airway hyperresponsiveness test to methacholine inhalation, the papain group showed significantly increased airway hyperresponsiveness and asthmatic features. Repeated papain-treated mice were shown to be a reasonable model for human ACO.

Free Research Field

呼吸器内科学

Academic Significance and Societal Importance of the Research Achievements

喘息・COPDオーバーラップ（ACO）については、重要な呼吸器疾患である一方、背景病態の理解はいまだ未解明である。本モデルは、小動物を用いて簡便に作成できる一方、COPDおよびヒト気管支喘息に相当する特徴も有することが示された。前述の通りヒトCOPDとしての特徴を持つことも合わせ、本研究におけるパパイン反復投与マウスはヒトACOを模したモデルとして妥当であると示された。