Antibody-dependent cytotoxicity: modulation by the cytochalasins and microtubule-disruptive agents

Cytochalasin B was shown to inhibit lysis of antibody-coated target cells by effector cells from rabbit spleen and lymph node. The inhibitory activity was dose-dependent and reversible. At low concentrations of cytochalasin B (0.15 to 0.3 mug/ml) enhancement of antibody-dependent cytotoxicity was observed. The drug appeared to act at an early stage of the lytic pathway after effector cell-target cell interaction, but before triggering of the cytotoxic event. Cytochalasin A was shown to be a more potent but similarly reversible inhibitor of antibody-dependent cytotoxicity. No enhancement of cytotoxicity was seen at non-inhibitory concentrations of cytochalasin A. The microtubule-disruptive agents colchicine (10-4 M), vinblastine (10-5 M) and colcemid (10-6 M) did not influence antibody-dependent cytotoxicity at concentrations which were not toxic to the effector cells. Our results suggest that antibody-dependent cytotoxicity is a surface membrane-initiated process and microtubule-associated functions are not essential.