Inflammatory events induced by Lys-49 and Asp-49 phospholipases A2 isolated from Bothrops asper snake venom: role of catalytic activity.
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.
Zuliani
Juliana P
JP
Laboratorio de Farmacologia, Instituto Butantan, Sao Paulo, Brazil.
Fernandes
Cristina M
CM
Zamuner
Stella R
SR
Gutiérrez
José M
JM
Teixeira
Catarina F P
CF
D000818:Animals; D017837:Bothrops; D002199:Capillary Permeability / Q000187:drug effects; D002384:Catalysis; D015815:Cell Adhesion Molecules / Q000502:physiology; D003435:Crotalid Venoms / Q000201:enzymology*; D015777:Eicosanoids / Q000378:metabolism; D007249:Inflammation / Q000139:chemically induced*; D007375:Interleukin-1 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D007962:Leukocytes / Q000187:drug effects; D008297:Male; D051379:Mice; D010741:Phospholipases A / Q000737:chemistry / Q000302:isolation & purification / Q000633:toxicity*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D015815:Cell Adhesion Molecules; D003435:Crotalid Venoms; D015777:Eicosanoids; D007375:Interleukin-1; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D010741:Phospholipases A