Disruption of oligosaccharide processing in murine tumor cells inhibits their susceptibility to lysis by activated mouse macrophages.
The components of tumor cell surfaces that participate in the recognition and lysis of these cells by activated macrophages have not been identified. One plausible hypothesis is that these components are specific carbohydrate structures. As an initial test of this hypothesis, I have made use of the oligosaccharide processing inhibitors 1-deoxynojirimycin (dNM) and 1-deoxymannojirimycin (dMM). dNM is an inhibitor of the glucosidases involved in the initial steps of oligosaccharide processing. dMM inhibits mannosidase I. P815 cells incubated in the presence of 1-2 mM dNM for 24 hr synthesized mature glycoproteins that contained glucosylated high-mannose asparagine-linked oligosaccharides instead of complex forms. The glucosylated oligosaccharides were present in trypsin digests of the cell surface. The dNM treatment resulted in a diminution in the amount of surface galactose residues as evidenced by neuraminidase/galactose oxidase/NaB3H4 labeling of surface glycopeptides. It did not, however, inhibit protein synthesis or alter the surface polypeptide profile of the tumor cells. P815 and R1- cells incubated in the presence of 1-3 mM dNM for 24 hr were considerably less sensitive to lysis by interferon-gamma-activated macrophages than were cells incubated in control medium. At a dNM concentration of 3 mM, a 71% inhibition of P815 cell lysis was observed. Similarly, P815 and R1- cells incubated in the presence of 2 mM dMM were also less sensitive to macrophage-mediated lysis than were control cells. The inhibitors did not affect cell viability, growth, or gross morphology. These observations suggest that complex asparagine-linked oligosaccharides on tumor cell surfaces may participate in recognition and lysis by activated macrophages.
D017485:1-Deoxynojirimycin; D000818:Animals; D002460:Cell Line; D005260:Female; D005944:Glucosamine / Q000031:analogs & derivatives / Q000494:pharmacology; D006023:Glycoproteins / Q000276:immunology / Q000378:metabolism*; D008264:Macrophages / Q000276:immunology*; D051379:Mice; D009363:Neoplasm Proteins / Q000276:immunology / Q000378:metabolism*; D009374:Neoplasms, Experimental / Q000276:immunology*; D011499:Protein Processing, Post-Translational / Q000187:drug effects
D006023:Glycoproteins; D009363:Neoplasm Proteins; D017485:1-Deoxynojirimycin; D005944:Glucosamine