Vaccinations with habu (Protobothrops flavoviridis) venom toxoid were administered to individuals living in Amami Oshima from 1965 to 2002, and its effectiveness was investigated in 1991. The results raised the possibility that normal human serum inherently contains an inhibitor of the hemorrhagic metalloproteinase HR2, considered to be one of the major components of habu venom. In this study, we investigated the interaction between the hemorrhagic metalloproteinases HR1 and HR2 from habu-venom and human alpha 2-macroglobulin (α2M). Hemorrhagic activity of HR2 was completely inhibited by human α2M. However, the hemorrhagic activity of the large molecule HR1a was not inhibited. Size exclusion chromatography revealed that human α2M captured the HR2 molecule and formed a complex with it, thus inhibiting hemorrhagic activity. These results suggest that human α2M plays an important role in the inhibition of hemorrhage induced by HR2 from habu venom.
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