TETANUS TOXIN SELECTIVELY IMPAIRS ANTI-TUMORAL BUT NOT ANTIMICROBIAL MACROPHAGE-MEDIATED EFFECTOR FUNCTIONS

The present study was designed to establish the susceptibility of macr ophage-mediated effector functions to tetanus toxin (TT). Using the mu rine macrophage cell line, GG2EE, generated in vitro by v-raf/v-myc on cogenes, we have previously provided evidence that TT selectively inhi bits interferon gamma (IFN-gamma), but not basal, lysozyme activity. H ere we show that while neither phagocytic nor candidacidal activities are affected by TT treatment, antitumoral activity is significantly im paired after exposure to TT. This phenomenon, which is dose-dependent, is fully ascribed to the holotoxin, as heat inactivated TT, C or A-B fragments result ineffective. Furthermore, C but not A-B fragment comp etes with TT in abrogating its inhibitory effects. Overall, these data indicate that TT is not a broad-spectrum, down-regulating signal on m acrophage-mediated functions, thus implying that its toxic action is e xerted on specific molecular targets.