Enhancement of macrophage-mediated tumor cell killing by bacterial outer membrane proteins (porins).
Various microbial products are known to influence the function of mouse peritoneal macrophages. Lipopolysaccharide (LPS) and certain lipid A-associated proteins are known to enhance the tumoricidal effects of macrophages. The purpose of this study was to determine whether porins (outer membrane proteins) of Salmonella typhimurium G30/C21 would influence the activity of macrophages from lipid A-responsive and -unresponsive mice. Porins, extracted by a combined sodium dodecyl sulfate-EDTA method from cell walls, were free of LPS as determined by Limulus amebocyte lysate assay and appeared as a band at approximately 36,000 molecular weight on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. In tumor cell killing assays done under LPS-free conditions, the porins in doses of 1 to 10 ng/ml enhanced the tumoricidal effect of macrophages from bacillus Calmette-Guérin-infected C3H/HeN or C3H/HeJ mice. Protein-free LPS enhanced the tumoricidal activity of macrophages from bacillus Calmette-Guérin-infected C3H/HeN but not C3H/HeJ mice. The tumoricidal-enhancing activity of protein-free LPS was blocked by the lipid A-binding antibiotic polymyxin B sulfate, but the effects of porins were not altered by the polymyxin B sulfate. These results suggest that porins, proteins known to alter membrane function, may alter macrophage function by interaction with macrophage membranes.
D000818:Animals; D001500:BCG Vaccine / Q000276:immunology; D001426:Bacterial Proteins / Q000494:pharmacology*; D002460:Cell Line; D003602:Cytotoxicity, Immunologic / Q000187:drug effects*; D005260:Female; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000276:immunology*; D008565:Membrane Proteins / Q000494:pharmacology*; D051379:Mice; D008809:Mice, Inbred C3H; D011112:Polymyxin B / Q000494:pharmacology; D018272:Porins; D012486:Salmonella typhimurium / Q000032:analysis; D012513:Sarcoma, Experimental / Q000276:immunology*
D001500:BCG Vaccine; D001426:Bacterial Proteins; D008070:Lipopolysaccharides; D008565:Membrane Proteins; D018272:Porins; D011112:Polymyxin B