Biotecnologia Aplicada Elfos Scientiae ISSN: 0684-4551 Vol. 14, Num. 1, 1997, pp. 44

THE INHIBITORY EFFECT OF TUMOR-SHED GANGLIOSIDES ON THE PRODUCTION OF IL-1BETA BY MONOCYTES AS WELL AS ON THE PROLIFERATIVE ACTIVITY OF THIS LYMPHOKINE ON THYMOCYTES DEPENDS ON THE STRUCTURES OF BOTH OLIGOSACCHARIDE AND CERAMIDE MOIETIES OF THE GANGLIOSIDES

Jacques Portoukalian

INSERM, Laboratory of Immunology and Experimental Oncology, Center Leon Berard, 69373 Lyon Cx 08, France.

Code Number:BA97008
Size of Files:
    Text: 2.7K
    Graphics: No associated graphics files

Gangliosides are sialic acid-containing glycosphingolipids made of an oligosaccharide bound to a ceramide moiety. These molecules are highly exposed at the cell surface of tumor cells and one of the mechanisms by which the tumors escape the immune system is thought to involve shedding of gangliosides from the cell surface into the extracellular medium and the subsequent uptake of shed gan gliosides by lymphocytes. Shedding is an active phenomenon closely related to the rate of proliferation and the amount of gangliosides released by tumor cells is equal after three to four days to the total cellular ganglioside content. At concentrations frequently found in the sera of tumor-bearing patients, the in vitro uptake of tumor-associated gangliosides during three days by monocytes leads to the insertion of these gangliosides in their plasma membrane. Such an enrichment of gangliosides results in a dramatic decrease in the production of IL-1 upon activation of monocytes by LPS. A study was carried out using several gangliosides known to be major components of various tumors and their effects were widely different. The production of IL-1 by LPS-activated monocytes was highly sensitive to gangliosides and GM2 had the most inhibitory effect whereas it had a very weak influence on the proliferative activity of IL-1 on thymocytes. At the opposite, GM3 showed a much more potent inhibition on the activity of IL-1 than on its production.

The potency of gangliosides as inhibitors of IL-1 production was in the decreasing order: GM2 > GD1a > 9-OAcGD3 > GD2 >> GT1b > GM3 > GD3 > GD1b. The study of these gangliosides as inhibi tors of IL-1 dependent thymoproliferation showed quite different effects and the order of potency was the following: 9-OAcGD3 > GM3 > GD2 > GD1b > GT1b > GD3 > GD1a > GM2. These results suggest that the extent of immunomodulation by tumor-shed gangliosides depends greatly on the ganglioside pattern of the tumors.

Copyright 1997 Elfos Scientiae