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The platelet glycoprotein thrombospondin binds specifically to sulfated glycolipids.

1985; Elsevier BV; Volume: 260; Issue: 16 Linguagem: Inglês

10.1016/s0021-9258(17)39381-x

1083-351X

David D. Roberts, Doris M. Haverstick, Vishva M. Dixit, William A. Frazier, Samuel A. Santoro, Victor Ginsburg,

Blood properties and coagulation

The human platelet glycoprotein thrombospondin (TSP) binds specifically and with high affinity to SUIfatides (galactosylceramide-13-sulfate).Binding of 1251-TSP to lipids from sheep and human erythrocytes and human platelets resolved on thin layer chromatograms indicates that sulfatides are the only lipids in the membrane which bind TSP.Binding to less than 2 ng of sulfatide could be detected.TSP failed to bind to other purified lipids i n c l u ~~n g cholesterol 3-sulfate, phospholipids, neutral glycolipids, and gangliosides.Binding of "'I-TSP was inhibited by unlabeled TSP, by low pH, and by reduction of intersubunit disulfide bonds with dithiothreitol.A monoclonal antibody against TSP (A2.5), which inhibits hemagglutination and agglutination of fixed activated platelets by TSP, strongly inhibited TSP binding to sulfatides.A second monoclonai antibody (C6.7), which inhibits hemagglutination and aggregation of thrombin-activated live platelets, weakly inhibited sulfatide binding.Binding was inhibited by high ionic strength and by some monosaccharide sulfates including methyl-a-~-GlcNAc-3sulfate.Neutral sugars did not inhibit.Fucoidan, a sulfated fucan, strongly inhibited binding with 50% inhibition at 0.3 pgfml fucoidan.Other sulfated polysaccharides including heparin and dextran sulfates were good inhibitors, whereas hyaluronic acid and keratan sulfate were very weak.The glycoprotein thrombospondin (TSP') is secreted from platelet a-granules following platelet activation (1, 2).TSP is also secreted and incorporated into the extracellular matrix by several cultured cell lines including endothelial (3-5) and smooth muscle ( 5 ) cells, fibroblasts (5, 6), and type I1 pneumocytes ('7).TSP binds to the surface of activated platelets and is responsible for their hemagglutinating activity (8).Blocking of platelet aggregation by low molecular weight inhibitors of TSP-mediated hemagglutination (9), by a monoclonal antibody to TSP (IO), and by polyclonal antibodies to