Cytotoxic mechanisms of bone marrow macrophages 145
Activation of cytotoxic activity in cultures of bone marrow-derived macrophages by indomethacin
Indomethacin was tested for its ability to augment the cytotoxic capacity of cultured bone marrow-derived macrophages ( M a ) against P815 and YAC-1 tumor cells. M@ were obtained from the bone marrow of C57BL16 mice precultured for 10-14 days and were virtually 100 percent pure. By addition of indomethacin these cells were activated to kill tumor cells in a 4-h and 18-h Cr-release assay. Since indomethacin is a potent inhibitor of the cyclooxygenase system, MQ, were treated with prostaglandin Ez. This treatment partially reversed indomethacin-induced cytotoxicity. Addition of other cyclooxygenase inhibitors such as acetyl-salicylic-acid, diclofenac or carprofen also induced cytotoxicity in bone marrow-derived M@. In all experiments we failed to detect any production of interferon. Addition of anti-interferon did not alter the cytolytic capacities demonstrating that endogenously induced interferon was not relevant in this mechanism. Our data show that cyclooxygenase inhibitors induce cytolytic activity of murine MQ, not only against a M@ target but also against YAC-1 cells usually considered to be targets for natural killer cells.