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The role of neutrophil extracellular traps in the pathogenesis of Kawasaki disease

Research Project

Project/Area Number 16K10082
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Pediatrics
Research InstitutionNational Defense Medical College

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)

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)
Project Period (FY) 2016-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
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)
Keywords川崎病 / 好中球 / 好中球細胞外トラップ / NETosis / 血管炎
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.

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。

Report

(5 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (21 results)

All 2020 2018 2017 2016

All Journal Article (5 results) (of which Int'l Joint Research: 4 results,  Peer Reviewed: 4 results,  Open Access: 4 results) Presentation (14 results) (of which Int'l Joint Research: 2 results) Book (2 results)

  • [Journal Article] Enhanced formation of neutrophil extracellular traps in Kawasaki disease2020

    • Author(s)
      Yoshida Yusuke、Takeshita Seiichiro、Kawamura Yoichi、Kanai Takashi、Tsujita Yuki、Nonoyama Shigeaki
    • Journal Title

      Pediatric Research

      Volume: - Issue: 6 Pages: 998-1004

    • DOI

      10.1038/s41390-019-0710-3

    • Related Report
      2019 Annual Research Report
  • [Journal Article] A comparison of the predictive validity of the combination of the neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio and other risk scoring systems for intravenous immunoglobulin (ivig)-resistance in Kawasaki disease.2017

    • Author(s)
      Takeshita Seiichiro, Kanai Takashi, Kawamura Yoichi, Yoshida Yusuke, Nonoyama Shigeaki
    • Journal Title

      PLoS One

      Volume: 12 Issue: 5 Pages: e0176957-e0176957

    • DOI

      10.1371/journal.pone.0176957

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] The role of neutrophil activation in the pathogenesis of Kawasaki disease2017

    • Author(s)
      Takeshita Seiichiro, Kawamura Yoichi, Kanai Takashi,Yoshida Yusuke, Nonoyama Shigeaki
    • Journal Title

      Pediatric Infectious Disease

      Volume: 3 Pages: 1-4

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Urinary Lactate Dehydrogenase Activity and Its Isozyme Patterns in Kawasaki Disease2017

    • Author(s)
      Kawamura Yoichi, Takeshita Seiichiro, Kanai Takashi, Takizawa Mari, Yoshida Yusuke, Tsujita Yuki, Nonoyama Shigeaki
    • Journal Title

      International Journal of Pediatrics

      Volume: 2017 Pages: 1-6

    • DOI

      10.1155/2017/4162597

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] The Combined Usefulness of the Neutrophil-to-Lymphocyte and Platelet-to-Lymphocyte Ratios in Predicting Intravenous Immunoglobulin Resistance with Kawasaki Disease2016

    • Author(s)
      Kawamura Yoichi, Takeshita Seiichiro, Kanai Takashi, Yoshida Yusuke, Nonoyama Shigeaki
    • Journal Title

      Journal of Pediatrics

      Volume: 178 Pages: 281-284

    • DOI

      10.1016/j.jpeds.2016.07.035

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] Trial of ulinastatin treatment for a murine model of Kawasaki Disease2018

    • Author(s)
      Tsujita Yuki, Kanai Takashi, Yoichi Kawamura, Nonoyama Shigeaki, Takeshita Seiichiro
    • Organizer
      The 12th International Kawasaki Disease Symposium
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Involvement of neutrophil extracellular traps in the pathogenesis of Kawasaki disease2018

    • Author(s)
      Yoshida Yusuke, Takeshita Seiichiro, Kawamura Yoichi, Kanai Takashi, Tsujita Yuki, Nonoyama Shigeaki
    • Organizer
      The 12th International Kawasaki Disease Symposium
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] 好中球細胞外トラップ(NETs)の川崎病の病態への関与2018

    • Author(s)
      吉田裕輔、竹下誠一郎、川村陽一、金井貴志、辻田由喜、野々山恵章
    • Organizer
      第121回日本小児科学会学術集会
    • Related Report
      2018 Research-status Report
  • [Presentation] 好中球/リンパ球比,血小板/リンパ球比によるIVIG不応の予測に関する多施設共同研究2018

    • Author(s)
      金井貴志、竹下誠一郎、川村陽一、木下恵司、中谷圭吾、岩島覚、瀧澤裕司、廣野恵一、森一越、吉田裕輔、野々山恵章
    • Organizer
      第121回日本小児科学会学術集会
    • Related Report
      2018 Research-status Report
  • [Presentation] ウリナスタチン併用療法プロトコールにおける冠動脈病変合併例の予後検討2018

    • Author(s)
      金井貴志、川村陽一、吉田裕輔、大澤麻登里、竹下誠一郎、野々山恵章
    • Organizer
      第38回日本川崎病学会・学術集会
    • Related Report
      2018 Research-status Report
  • [Presentation] 川崎病のIVIG不応予測因子としての好中球-リンパ球比と血小板-リンパ球比の有用性2017

    • Author(s)
      川村陽一, 金井貴志, 辻田由喜, 吉田裕輔, 竹下誠一郎, 野々山恵章
    • Organizer
      第120回日本小児科学会学術集会
    • Place of Presentation
      東京
    • Year and Date
      2017-04-15
    • Related Report
      2016 Research-status Report
  • [Presentation] 川崎病のIVIG不応予測因子としての好中球-リンパ球比と血小板-リンパ球比の有用性2017

    • Author(s)
      川村陽一、金井貴志、辻田由喜、吉田裕輔、竹下誠一郎、野々山恵章
    • Organizer
      第120回日本小児科学会学術集会
    • Related Report
      2017 Research-status Report
  • [Presentation] 川崎病急性期のIVIG不応予測における好中球/リンパ球比、血小板/リンパ球比の有用性:他のリスクスコアとの比較2017

    • Author(s)
      川村陽一、竹下誠一郎、金井貴志、辻田由喜、吉田裕輔、野々山恵章
    • Organizer
      第53回日本小児循環器学会総会・学術集会
    • Related Report
      2017 Research-status Report
  • [Presentation] 川崎病の病態における好中球細胞外トラップ(NETs)の関与について2017

    • Author(s)
      吉田裕輔、竹下誠一郎、川村陽一、金井貴志、辻田由喜、野々山恵章
    • Organizer
      第37回日本川崎病学会・学術集会
    • Related Report
      2017 Research-status Report
  • [Presentation] 好中球/リンパ球比、血小板/リンパ球比によるIVIG不応の予測に関する多施設共同研究2017

    • Author(s)
      金井貴志、竹下誠一郎、川村陽一、木下恵司、中谷圭吾、岩島覚、瀧澤裕司、廣野恵一、森一越、吉田裕輔、野々山恵章
    • Organizer
      第37回日本川崎病学会・学術集会
    • Related Report
      2017 Research-status Report
  • [Presentation] CAWS誘導川崎病類似マウス血管炎に対するウリナスタチンの効果について2017

    • Author(s)
      辻田由喜、金井貴志、吉田裕輔、川村陽一、三浦典子、大野尚仁、野々山恵章、竹下誠一郎
    • Organizer
      第37回日本川崎病学会・学術集会
    • Related Report
      2017 Research-status Report
  • [Presentation] 川崎病急性期の好中球/リンパ球比、血小板/リンパ球比はIVIG治療抵抗性の予測因子になりうるか?2016

    • Author(s)
      川村陽一, 金井貴志, 辻田由喜, 吉田裕輔, 竹下誠一郎, 野々山恵章
    • Organizer
      第52回日本小児循環器学会総会・学術集会
    • Place of Presentation
      東京
    • Related Report
      2016 Research-status Report
  • [Presentation] 川崎病急性期の好中球-リンパ球比、血小板-リンパ球比はIVIG 治療不応性の予測因子である2016

    • Author(s)
      金井貴志, 川村陽一, 辻田由喜, 吉田裕輔, 竹下誠一郎, 野々山恵章
    • Organizer
      第36回日本川崎病学会・学術集会
    • Place of Presentation
      横浜
    • Related Report
      2016 Research-status Report
  • [Presentation] CAWS誘導血管炎に対するウリナスタチン投与の検討2016

    • Author(s)
      辻田由喜, 金井貴志, 吉田裕輔, 川村陽一, 竹下誠一郎, 三浦典子, 大野尚仁, 野々山恵章
    • Organizer
      第60回日本医真菌学会総会・学術集会
    • Place of Presentation
      東京
    • Related Report
      2016 Research-status Report
  • [Book] Vasculitis (eBook), Chapter 1: Update on the immunomodulatory therapy for Kawasaki disease2017

    • Author(s)
      Takeshita Seiichiro, Kawamura Yoichi, Kanai Takashi
    • Publisher
      Avid Science
    • Related Report
      2017 Research-status Report
  • [Book] Kawasaki Disease. Current understanding of the mechanism and evidence-based treatment.2016

    • Author(s)
      Takeshita Seiichiro, Kawamura Yoichi, Kanai Takashi
    • Total Pages
      552
    • Publisher
      Springer
    • Related Report
      2016 Research-status Report

URL: 

Published: 2016-04-21   Modified: 2021-02-19  

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