Inhibition of platelet adhesion to fibronectin, fibrinogen, and von Willebrand factor substrates by complex gangliosides.
Gangliosides, which are complex glycosphingolipids containing sialic acid, are found in cell membranes and have been implicated in a variety of cell surface events including cellular adhesion. Complex gangliosides were observed to inhibit the adhesion of thrombin-activated platelets to substrates of fibronectin, von Willebrand factor, and fibrinogen. This adhesion, which is mediated by the glycoprotein IIb-IIIa complex, was differentially inhibited by gangliosides depending on the number of sialic acid residues present within the ganglioside. The observed order of effectiveness was GT1b greater than GD1a greater than GM1 greater than asialo-GM1. Another structurally related glycosphingolipid, globoside, exhibited little inhibitory activity. In contrast to the inhibition of platelet adhesion to von Willebrand factor mediated by the glycoprotein IIb-IIIa complex, gangliosides had no detectable effect on the ristocetin-dependent adhesion of platelets to von Willebrand factor mediated by glycoprotein Ib. These results suggest that the function of the glycoprotein IIb-IIIa complex may be modulated by gangliosides in a manner similar to that previously described for the closely related vitronectin receptor.
Santoro
S A
SA
Department of Pathology and Medicine, Washington University School of Medicine, St Louis, MO 63110.
D001792:Blood Platelets / Q000502:physiology; D005340:Fibrinogen / Q000502:physiology*; D005353:Fibronectins / Q000502:physiology*; D005732:Gangliosides / Q000097:blood / Q000502:physiology*; D006028:Glycosphingolipids / Q000097:blood / Q000502:physiology; D006801:Humans; D010973:Platelet Adhesiveness / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000097:blood / Q000502:physiology*; D010980:Platelet Membrane Glycoproteins / Q000502:physiology; D012310:Ristocetin; D013917:Thrombin; D014841:von Willebrand Factor / Q000502:physiology*
D005353:Fibronectins; D005732:Gangliosides; D006028:Glycosphingolipids; D010975:Platelet Aggregation Inhibitors; D010980:Platelet Membrane Glycoproteins; D014841:von Willebrand Factor; D012310:Ristocetin; D005340:Fibrinogen; D013917:Thrombin