title: 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.
abstract: 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.
mesh_terms: 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
chemical_list: D005231:Fatty Acids, Unsaturated; D008055:Lipids; D008070:Lipopolysaccharides; D008222:Lymphokines; D014280:Triglycerides