title: Phylogenetic conservation of a snake venom metalloproteinase epitope recognized by a monoclonal antibody that neutralizes hemorrhagic activity.
abstract: 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.
authors.affiliation: Laboratório de Imunopatologia, Instituto Butantan, Av. Vital Brasil, 1500, São Paulo, CEP: 05503-900, SP, Brazil.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Tanjoni
authors.forename: Diego
authors.initials: D
authors.lastname: Butera
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Spencer
authors.forename: Harumi A
authors.initials: HA
authors.lastname: Takehara
authors.forename: Irene
authors.initials: I
authors.lastname: Fernandes
authors.forename: Ana Maria
authors.initials: AM
authors.lastname: Moura-da-Silva
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology* / Q000494:pharmacology; D015153:Blotting, Western; D017837:Bothrops / Q000145:classification* / Q000235:genetics / Q000276:immunology; D017812:Colubridae / Q000235:genetics / Q000276:immunology; D003435:Crotalid Venoms / Q000737:chemistry / Q000201:enzymology / Q000235:genetics / Q000276:immunology* / Q000633:toxicity; D017815:Elapidae / Q000235:genetics / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D006470:Hemorrhage / Q000139:chemically induced / Q000276:immunology* / Q000517:prevention & control; D008666:Metalloendopeptidases / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D045726:Metalloproteases / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008969:Molecular Sequence Data; D010802:Phylogeny; D016415:Sequence Alignment; D017819:Viperidae / Q000235:genetics / Q000276:immunology; D000097146:Bothrops jararaca Venom
chemical_list: D000911:Antibodies, Monoclonal; D003435:Crotalid Venoms; D000939:Epitopes; D008666:Metalloendopeptidases; D045726:Metalloproteases; D000097146:Bothrops jararaca Venom