Human protein C inhibits selectin-mediated cell adhesion: role of unique fucosylated oligosaccharide.
The human anticoagulant factor, Protein C, is a plasma glycoprotein that 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 adhesion to vascular endothelial cells, which plays a critical role during inflammatory responses. We show that both human plasma-derived and human cell-produced recombinant Protein C inhibit E-selectin-mediated cell adhesion. This effect 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 structural 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 reported anti-inflammatory effects of Protein C and describe a new ligand for selectin-mediated adhesion.
Grinnell
B W
BW
Cardiovascular Research, Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN 46285-1543.
Hermann
R B
RB
Yan
S B
SB
D002236:Carbohydrate Conformation; D002240:Carbohydrate Sequence; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology*; D015815:Cell Adhesion Molecules / Q000502:physiology*; D002478:Cells, Cultured; D019040:E-Selectin; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D005643:Fucose / Q000032:analysis*; D006801:Humans; D008024:Ligands; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009844:Oligosaccharides / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D011486:Protein C / Q000737:chemistry* / Q000494:pharmacology*; D011994:Recombinant Proteins / Q000737:chemistry / Q000494:pharmacology; D014471:Umbilical Veins
D015815:Cell Adhesion Molecules; D019040:E-Selectin; D008024:Ligands; D009844:Oligosaccharides; D011486:Protein C; D011994:Recombinant Proteins; D005643:Fucose