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 metalloproteina se 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 gastrocn emius muscle. LHF-II degraded laminin, fibronectin and type IV collagen upo n 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 ind uced edema in the mouse footpad at doses where hemorrhage is absent. Inject ion of LHF-II induced the synthesis of matrix metalloproteinases evidenced in muscle homogenates and in exudate samples. It is concluded that LHF-II h as weak hemorrhagic and myotoxic activities, and that its role in the patho genesis of L. muta-induced local tissue damage is associated with edema for mation and degradation of extracellular matrix components, either directly or by activation. of endogenous matrix metalloproteinases. (C) 1999 Elsevie r Science Ltd. All rights reserved.