Characterization of the local tissue damage induced by LHF-II, a metalloproteinase with weak hemorrhagic activity isolated from Lachesis muta muta snake venom.
Local tissue damage induced by LHF-II, a 22-kDa hemorrhagic metalloproteinase from Lachesis muta venom was studied. Intravital microscopy experiments evidenced hemorrhagic events 2 min after LHF-II application onto cremaster muscle, characterized by microhemorrhages in capillary vessels and venules. However, histological analysis showed only mild hemorrhage in the gastrocnemius muscle. LHF-II degraded laminin, fibronectin and type IV collagen upon incubation in vitro, but was not cytotoxic to capillary endothelial cells in culture. Intramuscular injection of LHF-II induced a mild myonecrosis, with early small increments in plasma creatine kinase activity. It also induced edema in the mouse footpad at doses where hemorrhage is absent. Injection of LHF-II induced the synthesis of matrix metalloproteinases evidenced in muscle homogenates and in exudate samples. It is concluded that LHF-II has weak hemorrhagic and myotoxic activities, and that its role in the pathogenesis of L. muta-induced local tissue damage is associated with edema formation and degradation of extracellular matrix components, either directly or by activation of endogenous matrix metalloproteinases.
Instituto Clodomiro Picado, Facultad de Microbiologia, Universidad de Costa Rica, San José. arucavad@cariari.ucr.ac.cr
A
A
Rucavado
E
E
Flores-Sánchez
A
A
Franceschi
A
A
Magalhaes
J M
JM
Gutiérrez
D000818:Animals; D002196:Capillaries / Q000187:drug effects; D002478:Cells, Cultured; D003402:Creatine Kinase / Q000378:metabolism; D004487:Edema / Q000139:chemically induced; D005119:Extravasation of Diagnostic and Therapeutic Materials / Q000473:pathology; D005528:Foot / Q000502:physiology; D006470:Hemorrhage / Q000139:chemically induced* / Q000473:pathology; D007273:Injections, Intramuscular; D008666:Metalloendopeptidases / Q000633:toxicity*; D051379:Mice; D008833:Microcirculation / Q000187:drug effects*; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000473:pathology; D009336:Necrosis; D010447:Peptide Hydrolases / Q000494:pharmacology; D010741:Phospholipases A / Q000378:metabolism; D012910:Snake Venoms / Q000633:toxicity*; D014699:Venules / Q000187:drug effects; D017819:Viperidae / Q000502:physiology*
D012910:Snake Venoms; D003402:Creatine Kinase; D010741:Phospholipases A; D010447:Peptide Hydrolases; D008666:Metalloendopeptidases