Elucidation of a new neutrophil cell death mechanism by the cell adhesion regulator Rap1

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K06181
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 44010:Cell biology-related
• Research Institution: Kansai Medical University
• Principal Investigator: Kamioka Yuji 関西医科大学, 医学部, 講師 (50511424)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: shear flow / integrin / NETosis / Rap1 / mechanical stress / neutrophil

Outline of Final Research Achievements

In this research project, the generation of neutrophil-specific visualization mice and neutrophil-specific knockout mice were completed as planned. However, due to the malfunction of our two-photon laser microscope and other equipments, I was unable to achieve the planned in vivo and in vitro fluorescence imaging experiments. While there are challenges and problems in the reproducibility, data acquisition methods, and analysis methods for the quantitative image evaluation of NETosis, the advancement of image AI analysis technology is making it possible to train and classify a large number of images by commercially available softwares. Compared to the time of this project application, the benefits of developing an image classification program with my own hands have almost disappeared. But I have advanced the analysis under shear flow conditions that mimic physiological blood flow within blood vessels.

Free Research Field

細胞生物学

Academic Significance and Societal Importance of the Research Achievements

NETosisに関する研究報告は増加傾向であり、その分子メカニズムやいくつかの病態との関連についても新しい知見が増えてきている。一方で、生体または生体に近い環境下でNETosisを評価する手法は未だに不十分な状況である。本研究成果では血流環境下での細胞接着シグナルと細胞動態を評価することができた。血流流れ刺激を含めた新しい視点により、NETosis関連疾患の解明や創薬へ繋げられる可能性が出てきた。