| Project/Area Number |
18K08217
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 53040:Nephrology-related
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| Research Institution | Kitasato University |
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Principal Investigator |
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| 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)
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| Project Period (FY) |
2018-04-01 – 2022-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2021: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2020: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2019: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
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| 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 / 組織特異的マクロファージ / ネトーシス / 線維化 / 機能特異的マクロファージ / 間質性腎炎 / プログラム細胞死 |
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| 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.
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| 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。
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