Membrane vesicles shed by murine melanoma cells selectively inhibit the expression of Ia antigen by macrophages.
We previously demonstrated that membrane vesicles shed by the F10 variant of the murine B16 melanoma cell line inhibited the induction by interferon-gamma (IFN) of murine macrophage immune response region-associated (Ia) antigen expression. In this paper we present evidence that the inhibition of macrophage Ia antigen expression is a selective effect of vesicles and characterize its temporal requirements. Membrane vesicles shed from F10 cells did not affect the expression of macrophage H-2K or H-2D antigens under conditions shown to profoundly inhibit Ia antigen expression. Similarly, the induction of plasminogen activator and interleukin 1 from macrophages was not inhibited by the vesicles. The vesicles did not measurably decrease total cellular RNA or protein synthesis. Macrophages were sensitive to the inhibitory effects of the vesicles during the induction and maintenance phases of Ia expression. Pretreatment of macrophages with vesicles before culture with IFN did not reduce the induction of Ia. The rate of decline of Ia expression after removal of IFN was unaffected by the presence of vesicles. Removal of vesicles from cultures of IFN-treated macrophages resulted in only a partial recovery of Ia expression, suggesting that the inhibition of Ia expression may be a slowly reversible process. The selective and partially reversible inhibition of Ia expression by vesicles shed from the plasma membrane of tumor cells is a possible mechanism whereby tumor-bearing hosts may become immunocompromised.
Poutsiaka
D D
DD
Schroder
E W
EW
Taylor
D D
DD
Levy
E M
EM
Black
P H
PH
D000818:Animals; D002460:Cell Line; D002462:Cell Membrane / Q000276:immunology; D006224:Cricetinae; D003412:Cricetulus; D005260:Female; D005802:Genes, MHC Class II; D000949:Histocompatibility Antigens Class II / Q000032:analysis*; D007372:Interferons / Q000494:pharmacology; D007375:Interleukin-1 / Q000096:biosynthesis; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism; D008285:Major Histocompatibility Complex; D008297:Male; D008545:Melanoma / Q000276:immunology*; D051379:Mice; D008815:Mice, Inbred Strains; D010053:Ovary; D010960:Plasminogen Activators / Q000032:analysis; D014176:Protein Biosynthesis / Q000187:drug effects; D014158:Transcription, Genetic / Q000187:drug effects
D000949:Histocompatibility Antigens Class II; D007375:Interleukin-1; D007372:Interferons; D010960:Plasminogen Activators