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The venom of Micrurus lemniscatus , a coral snake of wide geographical distribution in South America, was fractionated by reverse-phase HPLC and the fractions screened for phospholipase A 2 (PLA 2 ) activity. The major component of the venom, a PLA 2 , here referred to as ‘Lemnitoxin’, was isolated and characterized biochemically and toxicologically. It induces myotoxicity upon intramuscular or intravenous injection into mice. The amino acid residues Arg15, Ala100, Asn108, and a hydrophobic residue at position 109, which are characteristic of myotoxic class I phospholipases A 2 , are present in Lemnitoxin. This PLA 2 is antigenically related to M. nigrocinctus nigroxin, Notechis scutatus notexin, Pseudechis australis mulgotoxin, and Pseudonaja textilis textilotoxin, as demonstrated with monoclonal and polyclonal antibodies. Lemnitoxin is highly selective in its targeting of cells, being cytotoxic for differentiated myotubes in vitro and muscle fibers in vivo , but not for undifferentiated myoblasts or endothelial cells. Lemnitoxin is not lethal after intravenous injection at doses up to 2 μg/g in mice, evidencing its lack of significant neurotoxicity. Lemnitoxin displays anticoagulant effect on human plasma and proinflammatory activity also, as it induces paw edema and mast cell degranulation. Thus, the results of this work demonstrate that Lemnitoxin is a potent myotoxic and proinflammatory class I PLA 2 . [ABSTRACT FROM AUTHOR]

The integrin αMβ2 regulates important cell functions in inflammation being the primary phagocytic receptor on macrophages. HF3, a metalloproteinase isolated from Bothrops jararaca venom, is a potent hemorrhagic toxin. A cDNA encoding HF3 indicated that it is a multidomain molecule composed of a pro-domain, a catalytic domain with a zinc binding sequence, followed by disintegrin-like and cysteine-rich domains. It is known that metalloproteinases play a relevant role in the pathogenesis of venom-induced local tissue damage including inflammation. In this study we evaluated the effects of native HF3 and its recombinant disintegrin-like/cysteine-rich domains (DC-HF3) on αMβ2-mediated phagocytosis of opsonized-zymosan particles by macrophages. HF3 and DC-HF3 significantly increased phagocytosis and this activity was inhibited by anti-αM and anti-β2 antibodies. The data show the ability of P-III metalloproteinases to activate macrophages for phagocytosis through integrin αMβ2 and suggest that the disintegrin-like/cysteine-rich domains are important for this effect. This is the first report on the activation of phagocytosis via αMβ2 integrin by a metalloproteinase containing disintegrin-like/cysteine-rich domains. [Copyright &y& Elsevier]