The unbalance between post-inflammatory apoptosis and NETosis possibly effects on the phagocyte which accelerate interstitial fibrosis in kidney

2021 Fiscal Year Final Research Report

• Project/Area Number: 18K08217
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 53040:Nephrology-related
• Research Institution: Kitasato University
• Principal Investigator: Takeuchi Yasuo 北里大学, 医学部, 教授 (60286359)
• Co-Investigator(Kenkyū-buntansha): 竹内 恵美子 北里大学, 医学部, 講師 (00406935) ; 川島 永子 北里大学, 医学部, 助教 (90342774)
• Project Period (FY): 2018-04-01 – 2022-03-31
• Keywords: 制御性細胞死 / 好中球 / 慢性肉芽腫症 / NETosis / Apoptosis / マクロファージ

Outline of Final Research Achievements

In this research, we analyzed the interaction between function-specific macrophages (SatM) isolated from the site of inflammation in the kidney and neutrophils which underwent Apoptosis / NETosis. In order to analyze　NOX2 sufficient/deficient cell death, several patterns of neutrophil cell death were quantified by measurement of the intensity of fluorescence of engulfed Zymosan or cleaved Caspase3 over 24 hours. As the results, NOX2 sufficient neutrophils, which engulfed Zymosan, die by apoptosis rather than NETosis. NETosis is thought to be strategy to kill extracellular pathogens, however, The inhibition of apoptosis made delay on clearance of fungal antigen. This is indicated that NETs may just trap pathogen but not kill them.

Free Research Field

臨床免疫学

Academic Significance and Societal Importance of the Research Achievements

好中球は細胞外に自己のDNAやタンパクなどを放出し、NETosisと呼ばれる方法で細胞外寄生性菌の分解、除去を行うと考えられてきた。しかし、我々が構築したin vitroの定量系によりNETosisよりもApoptosisを起こした方が排菌が速やかであり,NETosisには異物を拡散させないため捕捉する機能はあるが、分解の効率はApoptosisに及ばないことが示された。一方で、NETosisは様々な抗核抗体陽性自己免疫疾患の増悪に関わっていることは知られており、今後はNETosisをApoptosisへ誘導する治療が重要になることが予想できる。