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Sulfatides inhibit platelet adhesion to von Willebrand factor in flowing blood
Author(s) -
Borthakur G.,
Cruz M. A.,
Dong J. F.,
Mcintire L.,
Li F.,
López J. A.,
Thiagarajan P.
Publication year - 2003
Publication title -
journal of thrombosis and haemostasis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.947
H-Index - 178
eISSN - 1538-7836
pISSN - 1538-7933
DOI - 10.1046/j.1538-7836.2003.00156.x
Subject(s) - von willebrand factor , platelet adhesion , platelet , chemistry , adhesion , platelet adhesiveness , medicine , platelet aggregation , organic chemistry
Summary. Sulfatides are sulfated glycosphingolipids present on cell surfaces that bind to adhesive proteins such as von Willebrand factor (VWF), P‐selectin, laminin and thrombospondin. Previous studies have localized the sulfatide‐binding site of VWF to amino acid residues Gln626–Val646 in the A1 domain. The A1 domain also contains the binding site for platelet glycoprotein Ib (GP Ib), a site that has been reported to be distinct from the sulfatide‐binding site. In this study, we analyzed the interaction of sulfatides with VWF and its effect on GP Ib‐mediated platelet adhesion under flow conditions. Recombinant VWF A1 domain (rVWF‐A1) bound specifically and saturably to sulfatides (half‐maximal concentration of ∼12.5 µg mL −1 ), binding that was blocked by dextran sulfate (IC 50 ≈100 µg mL −1 ) but not by heparin at concentrations up to 100 U mL −1 . Furthermore, sulfatides (125 µg mL −1 ) prevented the adhesion of platelets or glycocalicin‐coupled polystyrene beads to a rVWF‐A1‐coated surface under high shear stress. In addition, plasma VWF prebound to a sulfatide‐coated surface failed to support subsequent platelet adhesion. These results provide firm evidence that sulfatides bind the VWF A1 domain at a site overlapping the GP Ib‐binding site.