Research on the relationship for heterogeneity of secretory granules with diversity of allergic responses

2021 Fiscal Year Final Research Report

• Project/Area Number: 19H03369
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 47030:Pharmaceutical hygiene and biochemistry-related
• Research Institution: Kanazawa University
• Principal Investigator: Suzuki Ryo 金沢大学, 薬学系, 教授 (00344458)
• Co-Investigator(Kenkyū-buntansha): 平嶋 尚英 名古屋市立大学, 医薬学総合研究院(薬学), 教授 (10192296)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: アレルギー / マスト細胞 / 開口放出 / 分泌顆粒 / 多様性

Outline of Final Research Achievements

Allergies are increasing in worldwide. There are many causes of allergy, and symptoms vary from mild to potentially life threatening. Mast cells (MCs) play an important role in allergic diseases. MCs contain many granules comprising various inflammatory mediators. However, the underlying mechanisms of the relationship between distinction of inflammatory mediator secretion in MCs and diversity of allergic reactions are still unknown. We observed the distribution of inflammatory mediators (e.g. TNFα, CCL2, or histamine) in the granules and different VAMPs, which is involved in mediator release. We found that each mediator and VAMP was located in different granules. Using VAMPs knockdown MC, we identified specific VAMP for b-hexosaminidase (i.e. histamine) release. Our observations suggested that each single granule contain specific inflammatory mediators. Thus, this may cause the diversity of allergic responses.

Free Research Field

アレルギー学、免疫学、分子細胞生物学

Academic Significance and Societal Importance of the Research Achievements

アレルギー疾患は、対処療法が中心となっている。その一因として、アレルギー疾患の多様な疾患症状が挙げられる。本研究は、アレルギー疾患の原因細胞あるマスト細胞での分泌顆粒における不均質性に着目し、アレルゲン刺激応答に伴う多様な分泌メカニズムについて、分子・細胞・生体レベルで明らかにすることを試みた。そして多様なアレルギー疾患の原因を解明し、新たな治療戦略へ繋げることが可能になると期待される。