Interferon-induced increase in neuraminidase-releasable sialic acid and glycosphingolipid metabolism in mouse lymphoma and L1210 leukemic cell lines: correlation with susceptibility to natural killer cell-mediated lysis.
Changes in sialoglycoconjugates and glycosphingolipid (GSL)5 metabolism were demonstrated in mouse EL4, P52 and YAC-1 lymphoma and L1210 leukemia cell lines treated with beta-interferon (IFN). Expression of cell surface (neuraminidase-releasable) sialic acid on IFN-treated cells was markedly elevated (three- to six-fold). The increase in neuraminidase-releasable sialic acid is contributed by sialoglycoproteins and particularly by cell-surface gangliosides in IFN-treated cells. Incorporation of [3H]-galactose into all GSL was elevated in IFN-treated cells. Thin-layer chromatographic analysis of GSL of IFN-treated cells showed an increase in several GSL homologues with striking changes in ganglioside with chromatographic migration of GM2, GM1, and GD1a relative to control cells. IFN-treated tumor-cell lines became resistant to lysis by virus-induced IFN-activated natural killer (NK) cells, as shown previously, but addition of neuraminidase to IFN-treated and untreated cells caused only a moderate increase in NK-sensitivity. This suggests that IFN-mediated protection of target cells from NK lysis was not due to a preferential masking of target structure by elevated levels of sialic acid. These membrane-associated changes in GSL and sialic acid in IFN-treated cells may be potentially significant, because a correlation between certain GSL expression, sialic acid phenotype and susceptibility of target cells to NK-cell-mediated lysis have been found in several other systems.
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D005690:Galactose / Q000378:metabolism; D006028:Glycosphingolipids / Q000378:metabolism*; D007370:Interferon Type I / Q000494:pharmacology*; D007694:Killer Cells, Natural / Q000276:immunology*; D007939:Leukemia L1210 / Q000378:metabolism*; D008223:Lymphoma / Q000378:metabolism*; D051379:Mice; D008815:Mice, Inbred Strains; D009374:Neoplasms, Experimental / Q000378:metabolism; D012794:Sialic Acids / Q000378:metabolism*
D006028:Glycosphingolipids; D007370:Interferon Type I; D012794:Sialic Acids; D005690:Galactose