Pharmacokinetics of phagocytes in phagocyte disorders

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K07807
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 52050:Embryonic medicine and pediatrics-related
• Research Institution: National Center for Child Health and Development
• Principal Investigator: Kawai Toshinao 国立研究開発法人国立成育医療研究センター, 生体防御系内科部, 医長 (20328305)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: 好中球 / 食細胞 / 遊走能 / 食細胞機能異常症 / 慢性肉芽腫症

Outline of Final Research Achievements

Phagocytes play central role in innate immunity, which are characterized by various functions including phagocytosis, production of reactive oxygen species, release of granule component and migration. The observation and continuous recording of phagocytic function can lead to assess the pharmacokinetics of phagocytes. In this study, we demonstrated the migration of neutrophils in response to the chemotactic factors.
Wiscott-Aldrich syndrome (WAS) is immunodeficiency disorder, characterized by the dysfunction of the dynamic remodelling of the actin-based cytoskeleton in migration. The neutrophil of WAS demonstrated less ability of migration. Chronic granulomatous disease (CGD) is characterized by a functional disorder of phagocytes to produce reactive oxygen species. In CGD, the migration of neutrophils in response to the chemotactic factors demonstrated the speed and acceleration similar to that of healthy control, however, CGD neutrophils migrated with multi-direction.

Free Research Field

感染免疫

Academic Significance and Societal Importance of the Research Achievements

本研究では、微小空間に化学物質の安定的な濃度勾配を形成し、化学物質に対する細胞の反応をリアルタイムに観察可能なライブイメージング技術を用いて、細胞動態を検討した。
慢性肉芽腫症は、食細胞の殺菌能が低下する原発性免疫不全症であるが、本疾患でみられる易感染性や過剰炎症などの機序について、不明な点が残されている。従来のボイデンチャンバー法では、遊走した細胞数を測定するだけの評価であった。しかし、本研究では、遊走の過程を画像的に解析することで、本疾患の好中球は様々に蛇行を繰り返して進むことが明らかになった。本解析は、他の食細胞機能異常症にも応用できる可能性があり、病態解明へ貢献し得ると考える。