Human Protein C inhibits selectin-mediated cell adhesion: role of unique fucosylated oligosaccharide

The human anticoagulant factor, Protein C, is a plasma glycoproteinthat has reported anti-ischaemic and anti-inflammatory properties.To explore potential mechanisms for these reported activities,we examined the effect of Protein C on the process of cell adhesionto vascular endothelial cells, which plays a critical role duringinflammatory responses. We show that both human plasma-derivedand human cell-produced recombinant Protein C inhibit E-selectin-mediatedcell adhesion. This effect was not mediated through the serineprotease activity of Protein C, but through its carbohydrates.Using oligosaccharides isolated from human cell-produced ProteinC, we have defined a polylactosamine structural determinantthat inhibits adhesion. This uncharged detenminant appears tobe a more potent ligand for E-selectin than the sialylated LewisX antigen. Our data suggest a potential mechanism for the reportedanti-inflammatory effects of Protein C and describe a new ligandfor selectin-mediated adhesion. cell adhesion fucosylated oligosaccharide human Protein C/PC-293 determinant selectin