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Investigation of the mechanism of low-affinity anti-histone H1 monoclonal antibody that rescues mice from lethal endotoxin shock

Research Project

Project/Area Number 26861531
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Emergency medicine
Research InstitutionJosai International University

Principal Investigator

Shimada Yayoi  城西国際大学, 大学共同利用機関等の部局等, 研究員 (70439024)

Project Period (FY) 2014-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2014: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywords抗-ヒストンH1抗体 / 抗-DNA抗体 / 多反応性抗体 / 抗体医薬 / 敗血症
Outline of Final Research Achievements

Anti-histone H1 monoclonal antibody (mAb) C93-3 has a low-affinity for histone H1 and rescues mice from lethal endotoxin shock. The purposes of this study were to identify other antigens of C93-3 and investigate its mechanism. We found that C93-3 is polyreactive and binds to α-actinin 1, α-actinin 4, nucleolin, hnRNP U and DNA. Administration of commercial anti-DNA mAb to mice underwent endotoxin shock improved survival rate. This result suggests that C93-3 suppresses inflammation by capturing extracellular DNA. Therefore, capturing extracellular DNA may be a potential treatment against severe sepsis.

Report

(3 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Research-status Report
  • Research Products

    (7 results)

All 2016 2015 2014 Other

All Int'l Joint Research (1 results) Journal Article (2 results) (of which Peer Reviewed: 2 results,  Open Access: 1 results) Presentation (4 results)

  • [Int'l Joint Research] Chang Gung Memorial Hospital(台湾)

    • Related Report
      2015 Annual Research Report
  • [Journal Article] The 24-hour in vitro hairless rat skin permeability study of the 1-day fentanyl transdermal formulations marketed in Japan - FentosTape and OneDuro Patch2016

    • Author(s)
      Yuichi Takizawa, Fumio Fukai, Takeshi Goto, Shuji Sato, Naoya Ohmori, Kenji Mori, Yayoi Shimada, Kuei-Chen Chiang, Takamitsu Miyagi
    • Journal Title

      Journal of Drug Delivery Research

      Volume: 印刷中

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A novel anti-histone H1 monoclonal antibody, SSV monoclonal antibody, improves lung injury and survival in a mouse model of lipopolysaccharide-induced sepsis-like syndrome2015

    • Author(s)
      Toru Kusano, Kuei-Chen Chiang, Masafumi Inomata, Yayoi Shimada, Naoya Ohmori, Takeshi Goto, Shuji Sato, Shigeru Goto, Toshiaki Nakano, Seiji Kawamoto, Yuki Takaoka, Norio Shiraishi, Takayuki Noguchi, and Seigo Kitano
    • Journal Title

      Biomed Research International

      Volume: 2015 Pages: 491649-491649

    • DOI

      10.1155/2015/491649

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] エンドトキシンショックからマウスを救命する多反応性モノクローナル抗体の作用機序の調査2015

    • Author(s)
      島田 弥生、江貴真、大森直哉、後藤武、佐藤秀次
    • Organizer
      第88回日本生化学会大会
    • Place of Presentation
      神戸ポートアイランド(兵庫県神戸市)
    • Year and Date
      2015-12-01
    • Related Report
      2015 Annual Research Report
  • [Presentation] Inhibition of DC maturation by SSV mAb: implication in inflammation and tolerance induction2014

    • Author(s)
      Kuei-Chen Chiang, Yayoi Shimada, Naoya Ohmori, Takeshi Goto and Shuji Sato
    • Organizer
      第43回日本免疫学会学術集会
    • Place of Presentation
      国立京都国際会館(京都府京都市)
    • Year and Date
      2014-12-10
    • Related Report
      2014 Research-status Report
  • [Presentation] 自己免疫疾患により誘導される抗ヒストンH1抗体の免疫抑制活性2014

    • Author(s)
      小田原駿介、小川誠、高岡勇輝、中野敏明、島田弥生、江貴真、大森直哉、後藤武、陳肇隆、後藤茂、小埜和久、河本正次
    • Organizer
      第5回癌と炎症とαリポ酸研究会
    • Place of Presentation
      ビーコンプラザ(大分県別府市)
    • Year and Date
      2014-11-15
    • Related Report
      2014 Research-status Report
  • [Presentation] 敗血症治療効果を有する抗-ヒストンH1モノクローナル抗体の交差抗原の探索2014

    • Author(s)
      島田弥生、江貴真、大森直哉、後藤武、佐藤秀次
    • Organizer
      第87回日本生化学会大会
    • Place of Presentation
      国立京都国際会館・グランドプリンスホテル京都(京都府京都市)
    • Year and Date
      2014-10-18
    • Related Report
      2014 Research-status Report

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Published: 2014-04-04   Modified: 2022-02-16  

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