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 phi) against P815 and YAC-1 tumor cells. M phi were obtained from the bone marrow of C57BL/6 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, M phi were treated with prostaglandin E2. 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 phi. 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 M phi not only against a M phi target but also against YAC-1 cells usually considered to be targets for natural killer cells.
D000818:Animals; D001854:Bone Marrow Cells; D002478:Cells, Cultured; D016861:Cyclooxygenase Inhibitors; D003601:Cytotoxicity Tests, Immunologic; D015232:Dinoprostone; D007213:Indomethacin / Q000494:pharmacology*; D007370:Interferon Type I / Q000502:physiology; D008262:Macrophage Activation / Q000187:drug effects*; D008264:Macrophages / Q000187:drug effects*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011458:Prostaglandins E / Q000494:pharmacology; D013268:Stimulation, Chemical
D016861:Cyclooxygenase Inhibitors; D007370:Interferon Type I; D011458:Prostaglandins E; D015232:Dinoprostone; D007213:Indomethacin