ROLE OF NITRIC OXIDE AND SIGNALING PATHWAYS MODULATING THE STIMULATORY EFFECT OF SNAKE VENOM SECRETORY PLA 2 S ON NON-OPSONIZED ZYMOSAN PHAGOCYTOSIS BY MACROPHAGES.

The phagocytic activity of macrophages activated with MT-II, a Lys-49 PLA2 homolog, and MT-III, an Asp-49 PLA2 , from Bothrops asper snake venom, was investigated in this study using a pharmacological approach. Stimulating thioglycollate-elicited macrophages with both venom components enhanced their ability to phagocytose non-opsonized zymosan particles. MT-II and MT-III-induced phagocytosis was drastically inhibited by pretreating cells with L-NAME, aminoguanidine or L-NIL, cNOS or iNOS inhibitors, or with ODQ (sGC inhibitor) or Rp-cGMPS (PKG inhibitor). These results indicate that the NO/sGC/GMP/PKG pathway plays an essential role in the β-glucan-mediated phagocytosis induced in macrophages by these venom-secretory PLA2 s.