Stimulation of macrophage activity by 12-O-tetradecanoylphorbol-13-acetate

Treatment of resident murine peritoneal macrophages with 12-O-tetradecanoyl phorbol-13-acetate (TPA) rapidly converted the cells to tumour cytostatic and cytolytic effector cells, as determined by growth inhibition or lysis of T-lymphoma cells (Eb, EL4) in vitro. The effective TPA concentrations were 10(-8) to 10(-7)M. Macrophages became cytotoxic as early as one to two hours after exposure to TPA, and tumour cytotoxicity persisted up to 48 hours. TPA did not interfere with the action of the lymphokine macrophage activating factor (MAF) but acted in synergy with it. Generation of antitumour-active macrophages by TPA was accompanied by other metabolic and functional changes, such as an enhancement of the hexose monophosphate shunt, glucosamine incorporation, RNA and protein synthesis, release of prostaglandin E2, thromboxane and prostacyclin, as well as pinocytosis. These data show that TPA may be a valuable model substance to complement studies of MAF; furthermore, use of TPA may help to clarify the role of activated macrophages during tumour promotion and tumour defense.