Cytotoxic activity of stimulated mouse macrophages exposed to various inhibitors.

Mouse peritoneal macrophages were cultured for 3 days with or without zymosan and at the same time exposed to various inhibitors of cellular metabolism. The cells were assayed for selective release of a lysosomal enzyme, and for cytotoxic activity against a tumor cell line, L-929-cells. Selective release of beta-glucuronidase was demonstrated in the supernatants from zymosan-stimulated macrophages. The stimulated macrophages were cytotoxic for the tumors cells, evaluated by measuring release of radioactivity during subsequent 4 days' co-culture of macrophages and 14C-thymidine-labelled tumor cells, and by counting cells per culture. Colchicine caused a slight, variable reduction in enzyme release and no change in cytotoxic effect from stimulated macrophages. Monensin decreased extracellular enzyme secretion and reduced the cytotoxicity in stimulated macrophages to control levels. Chloroquine caused a similar reduction in lysosomal enzyme release and cytotoxic activity in zymosan-stimulated cells. This inhibitor increased the enzyme release from control cells and induced a small, variable cytotoxic effect from these cells. The data indicate co-variation between macrophage-mediated cytotoxicity and a secretory process which can be blocked by monensin. The need for intact lysosomal function was also demonstrated.