Inhibition of Beta-Interferon Augmentation of Murine Natural Killer Cytoxicity by Gangliosides

Abstract

Interferons cause augmentation of natural killer (NK) cell activity, which might be a major reason for their antitumor effect. Antiviral and antigrowth effects of mouse β interferon are inhibited by mono-, di-, and trisialogangliosides commonly found in brain extracts, but also in membranes of many other cells. Results presented in this report show that preincubation of mouse β interferon with a brain ganglioside mixture or its isolated major components G_M1, G_D1b, G_D1b, and G_T1b (see Abbreviations) prior to addition to effector spleen cells, inhibits NK-cell enhancement due to interferon in a dosedependent manner. When spleen cells are treated with individual gangliosides alone, spontaneous NK cell activity is not affected. Pretreatment of effector cells with gangliosides prior to addition of interferon does not inhibit subsequent augmentation of NK cell activity by β interferon. Also, target susceptibility remains unaltered in the presence of gangliosides. Thus the inhibitory effect of gangliosides appears to involve competition for interaction of β interferon with the NK cells.