INHIBITORY EFFECT OF Crotalus durissus terrificus SNAKE VENOM (CdtV) OF MACROPHAGE PHAGOCYTOSIS. CONTRIBUTION OF CROTOXIN

SAMPAIO, SC(1), BRIGATTE, P(1), SANTOS, ACR.(2), SANTOS, EC.(2), SOUSA E SILVA, MCC.(1), CURI, R.(3), CURY, Y.(1)

(1)Laboratories of Pathophysiology and (2)Immunopathology; Butantan Institute, (3)Institute of Biomedical Sciences, USP, Brazil

Previous work from our laboratory has shown that, in addition to the opioid-mediated analgesic effect, CdtV inhibits phagocytic function of macrophages. The present work investigated: (a) the mechanisms responsible for the inhibitory effect of CdtV, and (b) the involvement of crotoxin (CTX), the main toxin of CdtV, in this effect. The CdtV, administered by sc route (30µg) to male Wistar rats or incubated with rat peritoneal resident macrophages inhibited phagocytosis of opsonized zymosan by these cells. The percentage of inhibition in the in vivo experiments was 46% and in the in vitro assays was: 0,25µg/ml-41%, 0,5µg/ml-44% and 1,0µg/ml-44%. Naloxone (1mg/kg) did not modifiedthe inhibitory effect of CdtV. On the other hand, neutralization of CdtV by specific antivenin blocked venom effect. Crotoxin, (19µg, sc) also inhibited (46%) the phagocytic activity of macrophages. This was a long lasting effect since it persisted for 14 days after CdtV administration. The inhibitory effect was also observed in vitro for CTX incubated (0,3; 0,016; 0,008 0,004µg/ml) with macrophages (30%; 33%; 47%; 53% of inhibition, respectively). The venom or CTX effect was not a consequence of a toxic effect, since FACS analysis did not show alterations of cell viability. These data suggest that the inhibitory effect of CdtV is not mediated by its opioid effect and demonstrate that CTX is involved with these inhibitory response.

Financial support: FAPESP and CNPq

CORRESPONDENCE TO:

Sandra Coccuzzo Sampaio, Rua Haroldo de Carvalho No. 46, São Paulo, SP, CEP: 04827140, Brasil, Email: sandracoccuzzo@yahoo.com