| Project/Area Number |
16K10082
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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 |
Pediatrics
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| Research Institution | National Defense Medical College |
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Principal Investigator |
TAKESHITA SEIICHIRO 防衛医科大学校(医学教育部医学科進学課程及び専門課程、動物実験施設、共同利用研究施設、病院並びに防衛, その他, 教授 (50369542)
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| Co-Investigator(Kenkyū-buntansha) |
川村 陽一 防衛医科大学校(医学教育部医学科進学課程及び専門課程、動物実験施設、共同利用研究施設、病院並びに防衛, 小児科学, 助教 (10648801)
野々山 恵章 防衛医科大学校(医学教育部医学科進学課程及び専門課程、動物実験施設、共同利用研究施設、病院並びに防衛, 小児科学, 教授 (40280961)
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| Project Period (FY) |
2016-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2016: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
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| Keywords | 川崎病 / 好中球 / 好中球細胞外トラップ / NETosis / 血管炎 |
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| Outline of Final Research Achievements |
Neutrophils contribute to the clearance of pathogens through the formation of neutrophil extracellular traps (NETs) in a process known as NETosis, but the excessive release of NETs has been reported to be involved in the pathogenesis of various diseases, including vasculitis, through inducing tissue injury. The aim of the present study was to investigate whether or not NETosis is enhanced in the acute phase of Kawasaki disease (KD). Spontaneous NET formation in vitro was observed in neutrophils isolated from KD patients, and the number of NET formations was significantly higher in acute KD than in convalescent KD and healthy children (HC). The increased levels of cell-free DNA (cfDNA) and neutrophil elastase (NE)-DNA complex in the acute phase of KD tended to decrease in the convalescent phase. Spontaneous NET formation was enhanced in neutrophils from patients with acute KD, suggesting the possible involvement of NETosis in the pathogenesis of KD vasculitis.
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| Academic Significance and Societal Importance of the Research Achievements |
KDではNETosisの制御機構が破綻することによってNETsの過剰な放出が起こり、血管炎の病態形成に深く関与することが予想される。KDの病態におけるNETs形成の関与を検討し制御機構を解明することによって、原因の究明・重症度判定・治療薬の新たな作用機序の解明に貢献することが可能であり、本研究の学術的な意義は大きい。申請者らはKDにおける活性化好中球の研究に長年携わっており、世界に先駆けて、NETs形成の動態に関する成果を発信することができると考える。
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