HUMAN PROTEIN-C INHIBITS SELECTIN-MEDIATED CELL-ADHESION - ROLE OF UNIQUE FUCOSYLATED OLIGOSACCHARIDE

The human anticoagulant factor, Protein C, is a plasma glycoprotein th at has reported anti-ischaemic and antiinflammatory properties. To exp lore potential mechanisms for these reported activities, we examined t he effect of Protein C on the process of cell adhesion to vascular end othelial cells, which plays a critical role during inflammatory respon ses. We show that both human plasma-derived and human cell-produced re combinant Protein C inhibit E-selectin-mediated cell adhesion. This ef fect was not mediated through the serine protease activity of Protein C, but through its carbohydrates. Using oligosaccharides isolated from human cell-produced Protein C, we have defined a polylactosamine stru ctural determinant that inhibits adhesion. This uncharged determinant appears to be a more potent ligand for E-selectin than the sialylated Lewis X antigen. Our data suggest a potential mechanism for the report ed anti-inflammatory effects of Protein C and describe a new ligand fo r selectin-mediated adhesion.