• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Drug development for sepsis by regulation of neutrophils

Research Project

Project/Area Number 25670464
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Infectious disease medicine
Research InstitutionOkayama University

Principal Investigator

NISHIBORI MASAHIRO  岡山大学, 医歯(薬)学総合研究科, 教授 (50135943)

Project Period (FY) 2013-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2014: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2013: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
KeywordsHRG / 敗血症 / ARDS / Immunothrombosis / 補充療法 / 組換えタンパク製剤 / 好中球 / 多臓器不全 / CLPモデル / 致死性
Outline of Final Research Achievements

Fundamental mechanisms for the preventive effects of purified human HRG on cecal-ligation and puncture (CLP)-induced sepsis in mice was examined.
Human HRG was purified from freshly frozen plasma by Ni-NTA affinity and MonoQ anion exchange chromatographies. Plasma levels of HRG in septic mice decreased dramatically to 20 % of sham control at 1 day after CLP and septic mice showed 100 % lethality. Treatment of mice with i.v. injection of purified human HRG at 20 mg/kg decreased the lethality significantly. HRG inhibited the adhesion of neutrophils on the lung microvasculatures, lung inflammation and DIC state, leading to the increase in survival rate. The treatment of isolated human neutrophils with HRG induced a spherical shape without microvilli and inhibited adhesion on vascular endothelial cells. HRG also strongly inhibited the production of reactive oxygen species. These results as a whole suggested that neutrophils are the target of HRG supplementary therapy for sepsis.

Report

(3 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Research-status Report
  • Research Products

    (18 results)

All 2015 2014 2013 Other

All Journal Article (5 results) (of which Peer Reviewed: 3 results,  Open Access: 1 results,  Acknowledgement Compliant: 1 results) Presentation (11 results) (of which Invited: 1 results) Patent(Industrial Property Rights) (2 results) (of which Overseas: 1 results)

  • [Journal Article] Glycyrrhizin inhibits traumatic brain injury by reducing HMGB1-RAGE interaction.2014

    • Author(s)
      OkumaY, Liu K, Wake H, Liu R, Nishimura Y, Zhong H, Teshigawara K, Haruma J, Yamamoto Y, Yamamoto H, Date I, Takahashi HK, Mori S, Nishibori M.
    • Journal Title

      Neuropharmacology

      Volume: 85 Pages: 18-26

    • DOI

      10.1016/j.neuropharm.2014.05.007

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Usefulness of high mobility group box 1 protein as a plasma biomarker in patient with peripheral artery disease.2014

    • Author(s)
      Oozawa S, Sano S, Nishibori M.
    • Journal Title

      Acta Med. Okayama

      Volume: 68(3) Pages: 157-162

    • NAID

      120005447128

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 抗HMGB1抗体治療の可能性-外傷性脳障害と神経因性疼痛に対する抗HMGB1抗体治療2014

    • Author(s)
      大熊 佑, 伊達 勲, 西堀正洋
    • Journal Title

      日薬理誌

      Volume: 143 Pages: 5-9

    • NAID

      130004827691

    • Related Report
      2013 Research-status Report
  • [Journal Article] Histamine inhibits high mobility group box 1-induced adhesion molecule expression on human monocytes2013

    • Author(s)
      Takahashi H、Sadamori H、Teshigawara K、Niwa A、Liu K、Wake H、Mori S、Yoshino T、Nishibori M
    • Journal Title

      Eur J Phamacol

      Volume: Vol.718、No.1-3 Issue: 1-3 Pages: 305-313

    • DOI

      10.1016/j.ejphar.2013.08.017

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] DAMPs:HMGB1の脳神経障害作用2013

    • Author(s)
      西堀正洋
    • Journal Title

      Thrombosis Medicine

      Volume: 3(4) Pages: 5-11

    • Related Report
      2013 Research-status Report
  • [Presentation] Plasma levels of Histidine-Rich Glycoprotein in Critically Ill Patients.2015

    • Author(s)
      Kuroda K, Morimatsu H, Wake H, Mori S, Nishibori M.
    • Organizer
      IARS 2015 Annual meeting and International Science Symposium
    • Place of Presentation
      The Hilton Hawaiian Village – Honolulu, Hawaii, USA.
    • Year and Date
      2015-03-21 – 2015-03-24
    • Related Report
      2014 Annual Research Report
  • [Presentation] 高ヒスチジン糖タンパク質(HRG)の敗血症時血管内好中球流動性に対する効果2015

    • Author(s)
      和氣秀徳、森秀治、高橋英夫、劉克約、勅使川原匡、西堀正洋
    • Organizer
      第88回日本薬理学会年会
    • Place of Presentation
      名古屋国際会議場(名古屋市)
    • Year and Date
      2015-03-18 – 2015-03-20
    • Related Report
      2014 Annual Research Report
  • [Presentation] SIRS患者におけるHistidine-Rich Glycoproteinについて2015

    • Author(s)
      黒田浩佐、森松博史、和氣秀徳、森秀治、西堀正洋
    • Organizer
      第42回日本集中治療医学会学術大会
    • Place of Presentation
      ホテル日航東京(東京都港区)
    • Year and Date
      2015-02-09 – 2015-02-11
    • Related Report
      2014 Annual Research Report
  • [Presentation] Histidine-rich glycoprotein prevents septic lethality through neutrophil regulation.2014

    • Author(s)
      Nishibori M, Wake H, Mori S, Liu K, Morioka Y, Teshigawara K, Sakagichi M, Kuroda K, Takahashi H, Ohtsuka A, Yoshino T, Morimatsu H.
    • Organizer
      SEPSIS 2014
    • Place of Presentation
      Institut Pasteur, Paris, France.
    • Year and Date
      2014-12-03 – 2014-12-05
    • Related Report
      2014 Annual Research Report
  • [Presentation] 循環好中球制御不全による敗血症性ARDSとHRG補充効果2014

    • Author(s)
      和氣秀徳、森秀治、劉克約、勅使川原匡、西堀正洋
    • Organizer
      第126回日本薬理学会近畿部会
    • Place of Presentation
      和歌山県JAビル(和歌山市)
    • Year and Date
      2014-10-24
    • Related Report
      2014 Annual Research Report
  • [Presentation] 好中球活性化制御に着目した敗血症病態解析と治療法開発2014

    • Author(s)
      和氣秀徳、森秀治、高橋英夫、劉克約、勅使川原匡、西堀正洋
    • Organizer
      第87回日本生化学会大会
    • Place of Presentation
      国立京都国際会館(京都市)
    • Year and Date
      2014-10-15 – 2014-10-18
    • Related Report
      2014 Annual Research Report
  • [Presentation] Endotoxin血症併発急性膵炎に対するHistidine Rich Grycoprotein (HRG) の効果2014

    • Author(s)
      寺尾欣也、和氣秀徳、森岡祐太、勅使川原匡、劉克約、森秀治、高橋英夫、西堀正洋
    • Organizer
      第125回日本薬理学会近畿部会
    • Place of Presentation
      岡山コンベンションセンター(岡山市)
    • Year and Date
      2014-06-20
    • Related Report
      2014 Annual Research Report
  • [Presentation] 新しい炎症制御機序と対外循環2014

    • Author(s)
      西堀正洋
    • Organizer
      第59回日本透析医学会学術集会・総会
    • Place of Presentation
      神戸ポートピアホテル(神戸市)
    • Year and Date
      2014-06-12 – 2014-06-15
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] 好中球の制御による敗血症、多臓器不全の治療法開発2014

    • Author(s)
      西堀正洋
    • Organizer
      BIO tech 2014 アカデミックフォーラム
    • Place of Presentation
      東京ビッグサイト(東京都江東区)
    • Year and Date
      2014-05-14 – 2014-05-16
    • Related Report
      2014 Annual Research Report
  • [Presentation] 血漿蛋白HRGによる好中球制御と敗血症治療薬開発

    • Author(s)
      西堀正洋、和氣秀徳、森秀治
    • Organizer
      第87回日本薬理学会年会
    • Place of Presentation
      仙台国際センター
    • Related Report
      2013 Research-status Report
  • [Presentation] 高ヒスチジン糖タンパク質(HRG)による敗血症治療の可能性

    • Author(s)
      和氣秀徳、森秀治、髙橋英夫、劉克約、勅使川原匡、西堀正洋
    • Organizer
      第87回日本薬理学会年会
    • Place of Presentation
      仙台国際センター
    • Related Report
      2013 Research-status Report
  • [Patent(Industrial Property Rights)] サイトカインストーム抑制剤2014

    • Inventor(s)
      西堀正洋、森秀治、和氣秀徳
    • Industrial Property Rights Holder
      岡山大学
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2014-258546
    • Filing Date
      2014-12-22
    • Related Report
      2014 Annual Research Report
  • [Patent(Industrial Property Rights)] 好中球活性化に起因する疾患の治療薬、治療方法及び検査方法2013

    • Inventor(s)
      西堀正洋、森秀治、和氣秀徳、髙橋英夫、劉克約、勅使川原匡
    • Industrial Property Rights Holder
      西堀正洋、森秀治、和氣秀徳、髙橋英夫、劉克約、勅使川原匡
    • Industrial Property Rights Type
      特許
    • Filing Date
      2013-05-28
    • Related Report
      2013 Research-status Report
    • Overseas

URL: 

Published: 2014-07-25   Modified: 2019-07-29  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi