Inflammatory events induced by Lys-49 and Asp-49 phospholipases A(2) isolated from Bothrops asper snake venom: role of catalytic activity

Autor(es)

Zuliani, Juliana P. ^[1] ; Fernandes, Cristina M. ; Zamuner, Stella R. ; Gutiérrez, José M. ; Teixeira, Catarina F. P.

Afiliação do(s) autor(es)

^[1] São Paulo (Estado). Secretaria de Estado da Saúde. Instituto Butantan. Laboratório de Farmacologia - Brasil

• Tipo de documento: Artigo Científico
• Fonte: Toxicon; v. 45, n. 3, p. 335-346, Mar. 2005.
• Área do conhecimento: Ciências Biológicas - Farmacologia
• Assunto(s): Farmacologia Toxinas em animal Venenos de origem animal Bothrops

Resumo

The inflammatory events induced in the peritoneal cavity of mice by two PLA(2)S isolated from Bothrops asper snake venom were investigated. MT-III, an Asp-49 catalytically active enzyme and MT-II, a catalytically inactive Lys-49 variant induced increase in vascular permeability. Inhibition of enzymatic activity of MT-III with p-bromophenacyl bromide reduced this effect. MT-III induced a larger neutrophil infiltrate than MT-II. This activity was significantly reduced after inhibition of catalytic activity. Reduction in the number of neutrophils was observed when antibodies against L-selectin, CD18 or LFA-1 were used, suggesting the involvement of these adhesion molecules in the effects of both PLA(2)s. There was no effect with antibodies against ICAM-1 and PECAM-1. Increase in the levels of LTB4 and TXA(2), as well as of IL-1, IL-6 and TNF-alpha, were observed in the peritoneal exudates induced by MT-III. MT-II did not enhance levels of eicosanoids but increased those of cytokines. It is concluded that both PLA(2)S induce inflammatory events in this model. Since MT-III exerts a stronger proinflammatory effect, the enzymatic phospholipid hydrolysis may be relevant for these phenomena. However, the fact that MT-II induced inflammation suggests that molecular regions distinct from the catalytic site elicit inflammatory events perhaps by interacting with specific cell membrane acceptors. (AU)

• Processo FAPESP: 98/00162-9 - Estudo dos mecanismos pro-inflamatorios induzidos pelos venenos de bothrops jararaca (america do sul) e bothrops asper (america central) em modelos experimentais in vivo e in vitro.
• Beneficiário: Catarina de Fatima Pereira Teixeira
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 98/15657-3 - Estudos de efeitos pro-inflamatorios induzidos por toxinas com estrutura de fosfolipase a2, isoladas do veneno de bothrops asper. recrutamento e ativacao leucocitaria.
• Beneficiário: Juliana Pavan Zuliani
• Modalidade de apoio: Bolsas no Brasil - Mestrado