The correlation between specific protein synthesis and tumoricidal function in murine peritoneal macrophages.
Macrophages from the lipopolysaccharide (LPS)-responsive C3H/HeN mouse strain and the closely related LPS-nonresponsive C3H/HeJ strain were compared for tumoricidal activation and protein synthetic changes following in vivo and in vitro stimulation, utilizing two-dimensional polyacrylamide gel electrophoresis of [35S]methionine-labeled proteins. Peritoneal macrophages elicited from C3H/HeN mice with heat-killed Propionibacterium acnes exhibited tumoricidal activity in a 16-hr cytolytic assay and expressed cytoplasmic levels of a 23.5-kDa protein during 48 hr of culture. The inability to detect persistent expression of p23.5 in P. acnes-stimulated C3H/HeJ macrophages correlated with the cytolytic impotence of those cells in the 16-hr chromium release assay. C3H/HeN macrophage populations lacking tumoricidal capacity could be rendered lytic, as could P. acnes-elicited C3H/HeJ macrophages, following in vitro stimulation with bacterial lipopolysaccharide. Concomitant with the LPS-induced expression of new functional activity was the appearance of augmented levels of several macrophage-specific proteins, including p23.5. This effect was dependent upon the lipid A moiety of LPS as the effects of LPS could be blocked by inclusion of polymyxin B sulfate in the culture medium. However, neither tumoricidal function nor protein modulation could be readily induced in C3H/HeJ proteose peptone-elicited or resident macrophages. These results identify biochemical responses to stimuli which may be requisite to acquisition or execution of cytolytic activity.
Tannenbaum
C S
CS
Temple University School of Medicine, Philadelphia, Pennsylvania.
Largen
M T
MT
D000818:Animals; D003602:Cytotoxicity, Immunologic / Q000235:genetics / Q000502:physiology*; D015180:Electrophoresis, Gel, Two-Dimensional; D007700:Kinetics; D008070:Lipopolysaccharides / Q000494:pharmacology; D008262:Macrophage Activation / Q000276:immunology; D008264:Macrophages / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D012515:Mast-Cell Sarcoma / Q000276:immunology; D051379:Mice; D008809:Mice, Inbred C3H / Q000276:immunology; D014176:Protein Biosynthesis / Q000187:drug effects
D008070:Lipopolysaccharides