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.
D000818:Animals; D000906:Antibodies; D002469:Cell Separation; D002645:Chickens / Q000276:immunology; D002860:Chromium Radioisotopes; D003078:Colchicine / Q000494:pharmacology*; D003571:Cytochalasin B / Q000494:pharmacology; D003572:Cytochalasins / Q000494:pharmacology*; D003601:Cytotoxicity Tests, Immunologic; D004121:Dimethyl Sulfoxide; D004912:Erythrocytes / Q000187:drug effects / Q000276:immunology; D008198:Lymph Nodes / Q000166:cytology; D008214:Lymphocytes / Q000187:drug effects* / Q000276:immunology; D008870:Microtubules / Q000276:immunology*; D011817:Rabbits; D013154:Spleen / Q000166:cytology; D014747:Vinblastine / Q000494:pharmacology*
D000906:Antibodies; D002860:Chromium Radioisotopes; D003572:Cytochalasins; D003571:Cytochalasin B; D014747:Vinblastine; D003078:Colchicine; D004121:Dimethyl Sulfoxide