Differential effects of prostaglandins on the antitumor activity of normal and BCG-activated macrophages

Abstract

The effect of exogeneously added prostaglandins E 1, E 2, and F 2α, on the capacity of normal and BCG-activated mouse peritoneal macrophages to destroy tumor cells, inhibit tumor cell proliferation, and phagocytize sheep red blood cells (SRBC) was assessed. BCG-activated macrophages destroyed the B16 melanoma cells as assessed by the release of tritiated thymidine ([ 3H]TdR). The addition of prostaglandins did not effect the tumoricidal activity of the macrophage. BCG-activated macrophages also inhibited the tumor cells from incorporating [ 3H]TdR while normal macrophages had no effect. The addition of prostaglandins to BCG-activated macrophages reduced their cytostatic effect on the tumor cells. In contrast, the growth inhibitory capacity of the normal macrophage was enhanced in the presence of prostaglandins. The effect of various pharmacological agents on the ability of the BCG-activated macrophage to reduce tumor cell growth was assessed. Indomethacin potentiated the prostaglandin-mediated reduction in tumoristatic activity. Dibutyryl cyclic AMP did not effect the antitumor activity of the macrophage. Prostaglandins of the E series and dibutyryl cyclic AMP inhibited the phagocytosis of SRBC by BCG-activated macrophages. The opposing effects of prostaglandins on the tumoristatic activity of the BCG-activated and normal macrophage suggests that prostaglandins may play a role in regulating macrophage function based on their level of activation.