FUMONISIN B-1 MODULATES SPHINGOMYELIN CYCLE PRODUCT LEVELS AND THE EXPRESSION OF CD3 RECEPTORS IN IMMUNOCOMPETENT ORGANS

The fungus Fusarium moniliforme, a parasite of cereals, produces abroa d range of mycotoxins, among which fumonisins are the most toxic and d isplay carcinogenic and teratogenic effects. Fumonisins inhibit the sy nthesis of sphingolipids; therefore, we studied the relationship betwe en the expression of the surface CD3 receptors of cells of immunocompe tent organs (spleen and thymus), which characterize T-cell-mediated im munity, and the extent of activation of the sphingomyelin cycle (chang es in sphingomyelinase activity and levels of sphingomyelin and cerami de) in these organs and liver 2.5 h after intraperitoneal administrati on of fumonisin B-1 (FB1; 5 or 20 mu g per mouse). Sphingomyelinase wa s significantly activated but the levels of sphingomyelin and ceramide s decreased in the thymus of animals injected:with 20 mu g of fumonisi n. The drug only slightly changed the activity of sphingomyelinase and the sphingomyelin level in the spleen and liver; however, the ceramid e level decreased significantly. Fumonisin strongly decreased the expr ession of CD3 receptors on the surface of thymocytes in vivo and in vi tro, which is consistent with the sharp decrease in the ceramide level in the organ. The accumulation of ceramide in thymocytes and splenocy tes treated with sphingomyelinase in vitro corresponds to an increase in the CD3 receptor affinity. A possible mechanism is discussed whereb y ceramides can mediate fumonisin-induced changes in the expression of receptors that modulate T-cell-mediated immunity.