Macrophage-mediated natural cytotoxicity of dimethyl sulfoxide-treated Friend erythroleukemia cells.

Dimethyl sulfoxide (DMSO) treatment of the Friend erythroleukemia cell line GM 979 markedly increased its susceptibility to natural cytotoxicity by splenocytes from normal inbred DBA/2 mice. Cytotoxicity occurred with normal adherent spleen cells as well as dextran-elicited peritoneal exudate (PE) cells but not with resident PE cells. Susceptibility of the leukemia cells to natural cytotoxicity increased to maximum levels upon treatment with 210 mM DMSO for 2-3 days. The natural cytotoxicity assayed by the 51Cr release procedure was first detectable after 9 hours of incubation and reached maximum levels by 24-30 hours. Although both DMSO and n-butyric acid induced rapid erythroid cell differentiation of the GM 979 cells, and both resulted in increased hemoglobin synthesis, only DMSO treatment enhanced the susceptibility of the cells to natural cytotoxicity by normal splenocytes. Cell-free supernatants from adherent spleen cells cocultured with DMSO-treated GM 979 cells for 6-15 hours were markedly cytotoxic for cultures of other chromium-labeled DMSO-treated leukemia cells. Supernatants from cultured adherent spleen cells alone, or lysates of DMSO-treated leukemia cells, did not possess cytotoxic activity. Resident peritoneal macrophages also had no cytotoxic activity against DMSO-treated cells, and culture supernatants from resident PE cells, even after incubation with DMSO-treated target cells, failed to show significant levels of cytotoxicity. These results indicate that normal splenic adherent cells as well as elicited PE cells have the ability to lyse DMSO-treated leukemia cells.