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

• Project/Area Number: 26861531
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Emergency medicine
• Research Institution: Josai 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: ¥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.

Research Products

• [Int'l Joint Research] Chang Gung Memorial Hospital(台湾)
• [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 Patch (2016)
  • 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
  • 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 syndrome (2015)
  • 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
  • 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
• [Presentation] Inhibition of DC maturation by SSV mAb: implication in inflammation and tolerance induction (2014)
  • 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
• [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
• [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