A carbohydrate domain common to both sialyl Le(a) and sialyl Le(X) is recognized by the endothelial cell leukocyte adhesion molecule ELAM-1.
The specificity of endothelial cell leukocyte adhesion molecule-1, ELAM-1, for binding to a panel of carbohydrate structures was determined by a sensitive cell binding assay with immobilized synthetic glycoconjugates. ELAM-1 cDNA transfectants were found to bind Sialyl Lea (sialylated lacto-N-fucopentaose II) or sialylated Lewis a antigen (NeuAc alpha 2-3Gal beta 1-3(Fuc alpha 1-4)GlcNAc), as well as or slightly better than Sialyl Lex (sialylated lacto-N-fucopentaose III) or sialylated Lewis X antigen (NeuAc alpha 2-3 Gal beta 1-4(Fuc alpha 1-3)GlcNAc). A monoclonal antibody, HECA-452, which has been identified recently as recognizing ELAM-1 ligands in addition to those containing Sialyl Lex, was also found to bind both Sialyl Lex and Sialyl Lea. Hard sphere exo-anomeric (HSEA) calculations were performed on these two hexasaccharides. The conformations indicate that Sialyl Lea and Sialyl Lex show a high degree of similarity in both the nonreducing and reducing termini. As Lea and Lex show much weaker reactivity, the determinants recognized by ELAM-1 and HECA-452 probably involve neuraminic acid and fucose residues which on one face of both Sialyl Lex and Sialyl Lea can be similarly positioned. The finding that Sialyl Lea is a potent ligand for ELAM-1 is important, as circulating Sialyl Lea and Sialyl Lex containing mucins which are elevated in the serum of many cancer patients may block leukocyte interactions with ELAM-1 and may contribute to the pathological immunodepression observed in these patients.
Berg
E L
EL
Department of Pathology, Stanford University, California 94305.
Robinson
M K
MK
Mansson
O
O
Butcher
E C
EC
Magnani
J L
JL
D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology / Q000378:metabolism; D001665:Binding Sites; D001667:Binding, Competitive; D050260:Carbohydrate Metabolism; D002240:Carbohydrate Sequence; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002460:Cell Line; D004247:DNA / Q000235:genetics; D019040:E-Selectin; D016256:Lewis X Antigen / Q000276:immunology / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D009844:Oligosaccharides / Q000276:immunology / Q000378:metabolism*; D014162:Transfection
D000951:Antigens, Neoplasm; D015815:Cell Adhesion Molecules; D019040:E-Selectin; D016256:Lewis X Antigen; D008562:Membrane Glycoproteins; D009844:Oligosaccharides; C058981:sialyl-Le(a) oligosaccharide; D004247:DNA