Human biliary mucin binds to E-selectin: a possible role in modulation of inflammation

E-selectin, expressed on endothelial cells, mediates adhesion of leukocytes and tumor cells to endothelium. CA19-9 (sialyl-Lewis(a)) and sialyl-Lewis( x) are specific ligands for E-selectin. We have recently shown that mucin-r ich culture media from human gallbladder epithelial cells contains CA19-9. In this study, we have tested whether human biliary mucin binds to E-select in. The ability of mucins to inhibit the adhesion of HL-60 cells to immobil ized E-selectin was taken as an index for E-selectin binding. Gallbladder b ile, hepatic bile, and culture medium from human gallbladder epithelial cel ls completely inhibited the adhesion of HL-60 cells to E-selectin. The muci n-rich fractions of human bile exhibited strong inhibition, whereas mucin-f ree fractions had little effect. In contrast to human bile samples, CA19-9- free medium from cultured dog gallbladder epithelial cells failed to inhibi t HL-60 binding. Furthermore, after CA19-9 immunoaffinity chromatography, w hich selectively extracted CA19-9 from bile, bile samples showed poor inhib ition of HL-60 adhesion to immobilized E-selectin. A good correlation was o bserved between E-selectin binding and CA 19-9 concentrations in bile. Our results show that human bile has E-selectin binding activity that is mediat ed by the CA19-9 side chain of biliary mucin.