Crotoxin, a rattlesnake toxin, induces a long-lasting inhibitory effect on phagocytosis by neutrophils

ABSTRACT

Crotalus durissus terrificus snake venom (CdtV) has long-lasting anti-inflammatory properties and inhibits the spreading andphagocytic activity of macrophages. Crotoxin (CTX), the main component of CdtV, is responsible for these effects.Considering the role of neutrophils in the inflammatory response and the lack of information about the effect of CdtV onneutrophils, the aim of this study was to investigate the effect of CdtV and CTX on two functions of neutrophils, namelyphagocytosis and production of reactive oxygen species, and on the intracellular signaling involved in phagocytosis,particularly on tyrosine phosphorylation and rearrangements of the actin cytoskeleton. Our results showed that theincubation of neutrophils with CdtV or CTX, at different concentrations, or the subcutaneous injection of CdtV or CTX inrats two hours or one, four or 14 days before or one hour after the induction of inflammation inhibited the phagocyticactivity of neutrophils. Furthermore, these in vitro and in vivo effects were associated with CdtV and CTX inhibition oftyrosine phosphorylation and consequently actin polymerization. Despite the inhibitory effect on phagocytosis, this study demonstrated that CdtV and CTX did not alter the production of the main reactive oxygen species. Therefore, this studycharacterized, for the first time, the actions of CdtV on neutrophils and demonstrated that CTX induces a long-lasting inhibition of tyrosine phosphorylation and consequently phagocytosis. We suggest that CTX represents a potential naturalproduct in controlling inflammatory diseases, since a single dose exerts a long-lasting effect on intracellular signaling involved in phagocytosis by neutrophils.