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.
Rucavado
A
A
Instituto Clodomiro Picado, Facultad de Microbiologia, Universidad de Costa Rica, San José. arucavad@cariari.ucr.ac.cr
Flores-Sánchez
E
E
Franceschi
A
A
Magalhaes
A
A
Gutiérrez
J M
JM
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