Inflammatory events induced by Lys-49 and Asp-49 phospholipases A2 isolated from Bothrops asper snake venom: role of catalytic activity

Toxicon. 2005 Mar 1;45(3):335-46. doi: 10.1016/j.toxicon.2004.11.004. Epub 2005 Jan 5.

Abstract

The inflammatory events induced in the peritoneal cavity of mice by two PLA2s 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 PLA2s. There was no effect with antibodies against ICAM-1 and PECAM-1. Increase in the levels of LTB4 and TXA2, 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 PLA2s 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bothrops
  • Capillary Permeability / drug effects
  • Catalysis
  • Cell Adhesion Molecules / physiology
  • Crotalid Venoms / enzymology*
  • Eicosanoids / metabolism
  • Inflammation / chemically induced*
  • Interleukin-1 / metabolism
  • Interleukin-6 / metabolism
  • Leukocytes / drug effects
  • Male
  • Mice
  • Phospholipases A / chemistry
  • Phospholipases A / isolation & purification
  • Phospholipases A / toxicity*
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Cell Adhesion Molecules
  • Crotalid Venoms
  • Eicosanoids
  • Interleukin-1
  • Interleukin-6
  • Tumor Necrosis Factor-alpha
  • Phospholipases A