Role of macrophage lipids in regulating tumoricidal activity. II. Internal genetic and external physiologic regulatory factors controlling macrophage tumor cytotoxicity also control characteristic lipid changes associated with tumoricidal cells.
Peritoneal macrophages (M phi) from C3H/HeN mice became cytotoxic for 1023 tumor cells after incubation with lymphokine (LK) for 8-12 hr and lost tumoricidal activity by 22 hr in the continued presence of LK; bacterial endotoxin (LPS) was ineffective in inducing tumoricidal activity. M phi from C3H/HeJ mice were not activated for tumor cytotoxicity after treatment with LK or LPS. C3H/HeN M phi acquisition of tumoricidal activity was accompanied by unique changes in M phi lipid composition: cellular content of cholesterol (CHOL) and polyunsaturated fatty acids (UFA) increased two- to threefold when the cells showed maximal tumoricidal activity and returned to control levels when the M phi lost tumoricidal activity. LPS treatment of C3H/HeN M phi and LK or LPS treatment of C3H/HeJ M phi did not cause characteristic M phi lipid alterations. To determine at what stage during M phi activation the correlative CHOL and UFA compositional changes were occurring, C3H/HeN M phi were primed with LPS or low concentrations of LK and triggered with LPS or Lk; M phi lipid and fatty acid composition was monitored at each stage. LK was shown to be able to prime and trigger whereas LPS could only trigger LK-primed M phi for tumor cytotoxicity. In all cases, the increase in M phi CHOL and UFA content occurred at the triggering step for tumor cytotoxicity rather than at the priming step. These data suggest that there is a correlation between the effects of endogenous and exogenous factors that control expression of M phi tumoricidal activity and their effects on M phi CHOL and UFA content; the establishment of these changes in M phi lipid composition occurs at a time when the cells are triggered for tumor cytotoxicity.
D000818:Animals; D003602:Cytotoxicity, Immunologic / Q000187:drug effects*; D005231:Fatty Acids, Unsaturated / Q000032:analysis; D008055:Lipids / Q000032:analysis / Q000502:physiology*; D008070:Lipopolysaccharides / Q000276:immunology; D008222:Lymphokines / Q000276:immunology*; D008262:Macrophage Activation; D008264:Macrophages / Q000032:analysis / Q000276:immunology*; D051379:Mice; D008967:Molecular Biology; D009374:Neoplasms, Experimental / Q000276:immunology; D014280:Triglycerides / Q000032:analysis
D005231:Fatty Acids, Unsaturated; D008055:Lipids; D008070:Lipopolysaccharides; D008222:Lymphokines; D014280:Triglycerides