INHIBITION OF IMMUNE CELL-PROLIFERATION AND CYTOKINE PRODUCTION BY LIPOPROTEIN-BOUND GANGLIOSIDES

We have analyzed the immunomodulatory effect of human melanoma ganglio sides bound to serum lipoprotein fractions on normal human immune-comp etent cells in vitro. Total melanoma gangliosides in micelles inhibite d proliferation of peripheral blood mononuclear cells stimulated by va rious mitogens, modulated lymphocyte surface molecules CD2, CD3, CD4, CD5 and CD8 and inhibited the production of interleukin-1 beta(IL-1 be ta), tumor necrosis factor alpha(TNF alpha) and IL-6 by stimulated adh erent cells. Most of these effects were abrogated in the presence of s erum. Purified serum lipoprotein fractions were tested for their abili ty to allow or inhibit the immunomodulatory effects of gangliosides. M elanoma gangliosides bound to very-low-density lipoproteins (VLDL) wer e shown to be as potent modulators of the immune response in vitro as when they were presented to cells in the form of micelles. Ganglioside s bound to low-density lipoproteins were less active and gangliosides bound to high-density lipoproteins or the lipoprotein-free fraction ha d no immunomodulatory effects. Given the fact that gangliosides are pr edominantly bound to lipoproteins in serum, we conclude that lipoprote ins are important determinants of the immunomodulating potential of tu mor gangliosides, and that the immunomodulatory effects of melanoma ga ngliosides observed in vitro may also occur in vivo.