We compared the effects of bryostatin 1 (BRYO), a non-tumor-promoting protein kinase C activator, and phorbol myristate acetate (PMA) on various types of lymphocyte cytotoxicity. An 18-h preincubation of lymphocytes with 10(-8) M BRYO inhibited natural killer (NK) activity but this inhibition was not statistically significant (p = 0.28). In contrast, NK activity was significantly enhanced by preincubation of lymphocytes with 10(-8) M PMA (p = 0.0012). Thus, in 13 experiments, the mean LU/10(6) was 21 +/- 12 for control cultured cells, 16 +/- 14 for BRYO cultured cells, and 40 +/- 22 for PMA cultured cells as determined in Cr-51-release assays with K562 target cells. Both BRYO and PMA inhibited lymphocyte antibody-dependent cell-mediated cytotoxicity (ADCC) such that, at a 20:1 effector-to-target ratio, control lymphocytes had a mean 49 +/- 12% specific Cr-51 release of antibody-coated target cells while BRYO and PMA cultured lymphocytes had 12 +/- 6 and 8 +/- 12%, respectively, in four experiments. The reduction in ADCC was paralleled by a decrease in Fc receptor (CD16) expression as determined by immunofluorescence analysis. We assessed the ability of BRYO and PMA to induce lymphokine-activated killer (LAK) activity by culturing lymphocytes with optimally mitogenic doses of these compounds and testing for cytotoxicity of Daudi target cells. While both BRYO and PMA induced [H-3]thymidine uptake, neither induced LAK activity. Furthermore, both compounds inhibited induction of LAK activity by recombinant interleukin-2 (rIL-2) in cocultures. We also analyzed the effect of BRYO and PMA on preactivated LAK effector cells. Lymphocytes were cultured for 3 days with 100 U/ml of rIL-2, aliquoted, and recultured for 18 h with rIL-2 alone and with the addition of 10(-8) M BRYO and 10(-8) M PMA, and then tested for LAK activity. Both compounds reduced the cytotoxic activity of LAK effector cells.
