1. ¹Laboratório de Imunoquímica, Instituto Butantan, São Paulo, Brazil
2. ²Department of Pharmacology, Therapeutics and Toxicology, Cardiff University, Wales College of Medicine, Cardiff, UK

Correspondence: Dr Denise V. Tambourgi, Laboratório de Imunoquímica, Instituto Butantan, Av. Professor Vital Brazil, 1500, São Paulo CEP 05508-900, Brazil. E-mail: dvtambourgi@butantan.gov.br

Received 26 April 2005; Revised 25 August 2005; Accepted 31 August 2005.

Abstract

Envenomation by the spider Loxosceles (brown spider) can result in dermonecrosis and severe ulceration. We have previously shown that Loxosceles sphingomyelinase D (SMaseD), the enzyme responsible for these pathological effects, induced expression of matrix metalloproteinase-9 (MMP-9), which is possibly one of the main factors involved in the pathogenesis of the cutaneous loxoscelism. The aim of this study was to further investigate the molecular mechanisms triggered by Loxosceles SMaseD involved in the initiation of the dermonecrotic lesion, using HaCaT cultures, a human keratinocyte cell line, as an in vitro model for cutaneous loxoscelism. We show here that SMaseD from Loxosceles spider venom induces apoptosis in human keratinocytes, which is associated with an increased expression of metalloproteinase-2 and -9, and that the use of metalloproteinase inhibitors, such as tetracycline, may prevent cell death and potentially may prevent tissue destruction after envenomation.