Role of membrane lipids in the immunological killing of tumor cells: II. Effector cell lipids

Peritoneal macrophages (MØ) from mice become cytotoxic after incubation in lymphokine (LK)-rich supernatants of antigen-stimulated spleen cell cultures. Tumoricidal activity is evident with MØ treated with LK for 4 hr, becomes maximal after 8–12 hr incubation and decreases to control levels by 24–36 hr. To gain insight into LK-induced functional changes, the lipid composition of MØ cultured with LK for 0–36 hr was analyzed by high pressure liquid chromatography. LK induced marked changes in MØ lipid composition: cellular content of cholesterol (CHOL) and polyunsaturated fatty acids increased 2- to 3-fold after 8 hr when the cells showed maximal tumoricidal activity. Cellular lipid and fatty acid content returned to control levels by 24 hr when the MØ had lost tumoricidal activity. These changes were not observed with equal numbers of MØ cultured in control supernatants. To analyze further the role of CHOL and unsaturated fatty acids in MØ tumor cytotoxicity, MØ were enriched in CHOL or linolenic acid (18∶3) and tested for their ability to kill 1023 tumor cells. Within 1 hr of culture, MØ showed a 3- to 4-fold increase in CHOL or 18∶3 content. 18∶3-enriched cells were markedly tumoricidal, whereas controls cultured in delipidized medium alone or enriched with saturated fatty acid were not cytotoxic. CHOL-enriched MØ were not tumoricidal; indeed, these cells were inhibited in their killing after treatment with LK compared to MØ cultured in delipidized medium with LK alone. These results suggest that UFA aids, whereas CHOL negates, expression of MØ tumor cytotoxicity.