Phylogenetic conservation of a snake venom metalloproteinase epitope recognized by a monoclonal antibody that neutralizes hemorrhagic activity.

Snake venom metalloproteinases (SVMPs) are present in large quantities in venoms of viper snakes and also in some elapids. Jararhagin is a representative of a P-III multidomain hemorrhagic SVMP present in Bothrops jararaca venom. It is comprised of a catalytic, a disintegrin-like and a cysteine-rich domain. Seven anti-jararhagin monoclonal antibodies (MAJar 1-7) were produced, of which six reacted with the disintegrin domain. MAJar 3 recognized an epitope present at the C-terminal part of the disintegrin-like domain, and neutralized jararhagin-induced hemorrhage. In this study, we evaluated the reactivity of these monoclonal antibodies with venoms from 27 species of snakes belonging to different families. MAJar 3 recognized most of the hemorrhagic venoms. By ELISA, MAJar 3 reacted strongly with venoms from Viperidae family and weakly with Colubridae and Elapidae venoms. This recognition pattern was due to bands between 50 and 80 kDa, corresponding to P-III SVMPs. This antibody preferentially neutralized the hemorrhage induced by venoms of Bothrops snakes. This fact suggests that the epitope recognized by MAJar 3 is present in other metalloproteinases throughout snake phylogeny. However, slight structural differences in the epitope may result in insufficient affinity for neutralization of biological activities.