Inhibition of human platelet aggregation by gangliosides

The content and composition of gangliosides is modified upon platelet stimu lation, suggesting that these lipids may play functional roles in platelet physiology. Therefore, the effect of exogenously added gangliosides on huma n platelet aggregation was evaluated. The pretreatment of platelets with a mixture of total gangliosides from bovine brain and a series of purified mo no-, di- and tri-sialogangliosides partially inhibit the collagen-induced a ggregation process and ATP release and completely block the generation of t he second aggregation wave when ADP is used as agonist, The inhibition was exerted at around 100 mu M by G(TOT) as well as purified G(M1), G(M3), G(D1 a), and G(T1b) gangliosides, whereas asialoG(M1) and sulphatide did not sho w a significant influence on platelet aggregation. Thrombin, Ca2+ ionophore s (A23187 and Ionomycin), arachidonic acid, and U46619 were unable to bypas s the inhibitory effect exerted by gangliosides, suggesting that gangliosid es inhibit platelet aggregation by inhibiting the synthesis or action of pr ostaglandins. Gangliosides inhibited U46619-induced aggregation, thus sugge sting that they block the action of thromboxane A(2). Epinephrine induces a partial aggregation on gangliosides-treated platelets, similar to fluoroal uminate and phorbol myristate acetate, indicating that these platelets are still functional. To summarize, these results indicate that the major pathw ay(s), but not all, driving to the aggregation process following the intera ction of ligand-receptor may be blocked by pretreatment of human platelets with gangliosides. (C) 2000 Elsevier Science Ltd. All rights reserved.