Received: June 18, 2007.

Accepted: November 9, 2007.

Abstract published online: November 13, 2007.

Full paper published online: March 8, 2008.

rACLF, A RECOMBINANT SNAKE VENOM METALLOPROTEASE, ACTIVATES ENDOTHELIAL CELLS IN VITRO

DE MORAES C. K. (1), FRITZEN M. (2), CHUDZINSKI-TAVASSI A. M. (2), SELISTRE-DE-ARAÚJO H. S. (1)

(1) Department of Physiological Sciences, Federal University of São Carlos, São Carlos, São Paulo State, Brazil; (2) Laboratory of Biochemistry and Biophysics, Butantan Institute, São Paulo, São Paulo State, Brazil.

ABSTRACT: Snake venom metalloproteases (SVMPs) comprise a family of snake venom toxins responsible for most of local and systemic effects observed during envenomation by snakes from the Viperidae family. The vascular system and more specifically the endothelium seem to be the preferential targets of these proteins. This work describes the effects of rACLF, a recombinant SVMP from Agkistrodon contortrix laticinctus on human umbilical vein endothelial cells (HUVECs) in vitro. Our results showed that rACLF activates HUVECs by the release of mediators involved in inflammation and hemostasis such as prostacyclin and interleukin-8. We also demonstrated that rACLF increased the expression of ICAM-I and decay accelerating factor (DAF). Moreover, rACLF protects the HUVECs against apoptosis induced by serum deprivation. These results suggest that the endothelial cell activation induced by SVMPs may have a significant role in the development of the local inflammatory lesion observed in Viperidae envenomation.

KEY WORDS: rACLF, snake venom metalloprotease, endothelial cells, inflammation.

CONFLICTS OF INTEREST:  There is no conflict.

CORRESPONDENCE TO:

HELOÍSA S. SELISTRE-DE-ARAÚJO, Departamento de Ciências Fisiológicas, Universidade Federal de São Carlos, São Carlos, SP, Brasil. Fax: + 55-16-3351-83-27. Email: hsaraujo@power.ufscar.br.