Effects Of Bothrops jararaca (BjV) And Crotalus durissus terrificus (CdtV) Snake Venoms  On Aminopeptidases Of Isolated Macrophages (MØ).

Olivo, R.A.; Nascimento, N.G.; Silveira, P.F.; Teixeira, C.F.P.

Laboratório de Farmacologia, Instituto Butantan, SP, Brasil.

Aminopeptidases (APs) constitute a family of enzymes relevant for cell adhesion and modulation of the activity of inflammatory mediators released from MØ. In this study we evaluated the in vitro effect of BjV and CdtV on the activities of soluble (S) and membrane-bound (M) neutral AP/CD13 (APN), basic AP (APB) and dipeptidyl peptidase IV/CD26 (DPPIV) in MØ. Peritoneal MØs were collected 96h after injection of 3% thioglycollate into peritoneum of male Swiss mice. 4x10⁶ MØ/mL were then incubated with non-cytotoxic concentrations of BjV (5mg/mL) or CdtV (1.5mg/mL) or PBS (control) for 1 h. The activities of APs were measured by fluorogenic assay using naphthylamide-derivative substrates. Results showed that DPPIV activity in S fraction was significantly reduced by both venoms while that of M fraction was increased by BjV but not CdtV. S-APN activity was significantly reduced by CdtV but not affected by BjV. In contrast, both venoms did not modify M-APN and S-APB activities. These data demonstrate that the effects caused by BjV on MØ aminopeptidases differ from those of CdtV. BjV induces dual effect on DPPIV activity, depending on the cellular location of this enzyme. The effect of BjV on soluble DPPIV may be related to the release of INF-g induced by this venom. The reduction of S-APN activity by CdtV may be relevant for the inhibitory effect of this venom on spreading and phagocytic activities of MØs.

Financial support: FAPESP

Correspondence to: renataolivo@butantan.gov.br