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-rich culture media from human gallbladder epithelial cells contains CA19-9. In this study, we have tested whether human biliary mucin binds to E-selectin. The ability of mucins to inhibit the adhesion of HL-60 cells to immobilized E-selectin was taken as an index for E-selectin binding. Gallbladder bile, hepatic bile, and culture medium from human gallbladder epithelial cells completely inhibited the adhesion of HL-60 cells to E-selectin. The mucin-rich fractions of human bile exhibited strong inhibition, whereas mucin-free fractions had little effect. In contrast to human bile samples, CA19-9-free medium from cultured dog gallbladder epithelial cells failed to inhibit HL-60 binding. Furthermore, after CA19-9 immunoaffinity chromatography, which selectively extracted CA19-9 from bile, bile samples showed poor inhibition of HL-60 adhesion to immobilized E-selectin. A good correlation was observed between E-selectin binding and CA 19-9 concentrations in bile. Our results show that human bile has E-selectin binding activity that is mediated by the CA19-9 side chain of biliary mucin.
Sreejayan
N
N
Department of Medicine II, Ludwig Maximilians University, Klinikum Grosshadern, D 81377 Munich, Germany.
Wittig
B M
BM
von Stillfried
N
N
Hennicke
M S
MS
Meyer
G
G
Stieber
P
P
Lamerz
R
R
von Ritter
C
C
D000818:Animals; D001646:Bile / Q000502:physiology*; D018395:CA-19-9 Antigen / Q000378:metabolism*; D002448:Cell Adhesion; D002478:Cells, Cultured; D002846:Chromatography, Affinity; D017077:Culture Media, Conditioned; D004285:Dogs; D019040:E-Selectin / Q000378:metabolism*; D004847:Epithelial Cells / Q000166:cytology / Q000502:physiology; D005704:Gallbladder / Q000166:cytology / Q000502:physiology; D018922:HL-60 Cells; D006801:Humans; D007249:Inflammation / Q000503:physiopathology*; D008024:Ligands; D009077:Mucins / Q000502:physiology*; D011993:Recombinant Fusion Proteins / Q000378:metabolism
D018395:CA-19-9 Antigen; D017077:Culture Media, Conditioned; D019040:E-Selectin; D008024:Ligands; D009077:Mucins; D011993:Recombinant Fusion Proteins