Decreased thrombin affinity of cell-surface thrombomodulin following treatment of cultured endothelial cells with β-D-xyloside

Thrombomodulin, an endothelial cell-surface anticoagulant, has been postulated to contain a glycosaminoglycan. Thrombomodulin function was therefore studied in endothelial cells treated with β-D-xyloside, an inhibitor of glycosaminoglycan attachment to proteoglycan core proteins. β-D-xyloside caused a reproducible 3 to 5-fold increase in the K_m of thrombomodulin for thrombin and a 20-30% decrease in the rate of protein C activation by the thrombin-thrombomodulin complex. These results support a role for glycosaminoglycans in thrombomodulin function and suggest that β-D-xylosides can be used to investigate both the anticoagulant mechanisms and the biosynthesis of cell-surface thrombomodulin.