2021 Fiscal Year Final Research Report
Regulation of sepsis by alarmin that induces the release of ectosomes with antibacterial potential from neutrophils
| Project/Area Number |
17K08840
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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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| Research Field |
Bacteriology (including mycology)
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| Research Institution | Juntendo University |
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Principal Investigator |
Nagaoka Isao 順天堂大学, 保健医療学部, 特任教授 (60164399)
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| Co-Investigator(Kenkyū-buntansha) |
桑原 京子 順天堂大学, 医学部, 非常勤講師 (10167976)
射場 敏明 順天堂大学, 医学部, 教授 (40193635)
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| Project Period (FY) |
2017-04-01 – 2022-03-31
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| Keywords | 好中球 / エクトソーム / 敗血症 / 抗菌ペプチド / LL-37 / 細胞外小胞 / アラーミン |
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| Outline of Final Research Achievements |
Neutrophils release microvesicles (ectosomes) upon stimulation. Interestingly, ectosome level is elevated in sepsis survivors. Previously, we revealed that LL-37, an antimicrobial peptide, improves the survival of septic mice. In the present study, we elucidated the action of LL-37 on septic mice, by focusing on the release of ectosomes from neutrophils. The results revealed that the ectosome level was enhanced by LL-37-administration, accompanied with reduced bacterial load. Importantly, ectosomes from LL-37-injected septic mice contained antimicrobial proteins/peptides, suggesting that LL-37 induces the release of antibacterial ectosomes. In fact, LL-37 stimulated mouse neutrophils to release antibacterial ectosomes. Furthermore, the administration of ectosomes reduced the bacterial load and improved the survival of septic mice. These observations suggest that LL-37 induces the release of antibacterial ectosomes, thereby reducing the bacterial load and protecting mice from sepsis.
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| Free Research Field |
生体防御学
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| Academic Significance and Societal Importance of the Research Achievements |
エクトソームは、敗血症において増加し、宿主細胞機能を変調させることから、敗血症治療の新たな標的として近年注目されている。申請者は、これまで、生体内抗菌ペプチドであるLL-37の宿主細胞に対する作用を解明してきたが、今回、LL-37が好中球を刺激して、抗菌活性をもつエクトソームの放出することで敗血症の病態改善に関与することを明らかにした。本研究の成果は、新たな視点で、生体内抗菌ペプチドの働きを解明したばかりでなく、将来、抗菌ペプチドを用いた安全かつ有効な敗血症治療法を開発するために有用な情報を提供するという点において意義深いと考える。
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