Oxygen-mediated mast cell activation in oxygen-induced anaphylaxis

2020 Fiscal Year Final Research Report

• Project/Area Number: 19K15977
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 42020:Veterinary medical science-related
• Research Institution: University of Tsukuba (2020); Tokyo University of Agriculture and Technology (2019)
• Principal Investigator: Matsuda Kenshiro 筑波大学, 革新的創薬開発研究センター, 研究員 (70642619)
• Project Period (FY): 2019-04-01 – 2021-03-31
• Keywords: アナフィラキシー / マスト細胞 / TRPA1 / 酸素

Outline of Final Research Achievements

Rapid shift of chronic hyperoxia to normoxia (relative hypoxia) induced systemic anaphylaxis in adult mice, however, anaphylactic response was inhibited in mast cell-deficient mice after relative hypoxic stimulation. Moreover, plasma histamine, tryptase, and beta-hexosaminidase release were also reduced in mast cell-deficient mice. These findings demonstrated that mast cell was the main regulator of oxygen-induced anaphylaxis.
To investigate how mast cell regulate oxygen-induced anaphylaxis, bone marrow-cultured mast cell (BMMC) was stimulated by relative hypoxia. After relative hypoxic stimulation, histamine, tryptase, and beta-hexosaminidase release were reduced in TRPA1-deficient BMMC as compared with wild type BMMC.
These results suggested that mast cell is the main mediator of oxygen-induced anaphylaxis, and TRPA1 regulate mast cell activation through relative hypoxic stimulation.

Free Research Field

Immunology

Academic Significance and Societal Importance of the Research Achievements

アナフィラキシーは、食物、医薬品や昆虫刺咬などのアレルゲン侵入の他、運動や温度などもトリガーとなる全身性アレルギー反応で、特に免疫学的機序を介さない、直接的にマスト細胞を活性化させるアナフィラキシーはその原因の特定が急務であった。本研究では、相対的低酸素刺激による非免疫学的機序に基づく新たなマスト細胞の活性化メカニズムを明らかにし、酸素が新たなアナフィラキシーの誘導因子である事を見出した。この事から相対的低酸素状況が想定される純酸素療法や急性高山病などの酸素起因性疾患は、アナフィラキシーを惹起するリスクがあり、その予防方法や治療方法提言のための基礎的知見として学術的意義を有する。