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

2015 Fiscal Year Final Research Report

• 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
• 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.

Free Research Field

分子生物学