Spectrum of sialylated and nonsialylated fuco-oligosaccharides bound by the endothelial-leukocyte adhesion molecule E-selectin. Dependence of the carbohydrate binding activity on E-selectin density.

Valency Dependent Patterns of Binding of Human L-Selectin toward Sialyl and Sulfated Oligosaccharides of Lea and Lex Types: Relevance to Anti-Adhesion Therapeutics

“…Under similar experimental conditions, the rat L-selectin also bound strongly to the sulfated ligands but gave little binding to the sialyl ligands (Green et al, 1995). Although direct comparisons cannot be made with human E-selectin on account of different experimental designs (Larkin et al, 1992;Yuen et al, 1994), there appears to be a marked difference in the relative intensities of binding of the human L-and E-selectins to the sulfated and sialyl ligands. Contrasting with the selective binding of the L-selectin to sulfated Le a and sulfated Le x pentasaccharides, Chinese hamster ovary cells expressing E-selectin either at high or at low density, bound to the sialyl-Le a and -Le x on chromatograms in addition to sulfated forms (the latter two were tested with the high density selectin only).…”

“…Contrasting with the selective binding of the L-selectin to sulfated Le a and sulfated Le x pentasaccharides, Chinese hamster ovary cells expressing E-selectin either at high or at low density, bound to the sialyl-Le a and -Le x on chromatograms in addition to sulfated forms (the latter two were tested with the high density selectin only). A further difference between the human E-and L-selectins is that the high-density (but not the low-density) E-selectin cells bound also to the non-sulfated, non-sialylated Le a and Le x pentasaccharides (Larkin et al, 1992). As differences in adhesion to immobilized low-affinity oligosaccharide ligands (Le a and Le x pentasaccharides) have been documented in experiments with the Chinese hamster ovary cells that expressed differing levels of membraneassociated E-selectin (Larkin et al 1992), we suggest that the differences observed here in L-selectin binding to the higher and lower affinity ligands (sulfated and sialyl, respectively) are likely to be manifest in ViVo where the selectin is expressed on the microvilli of leukocyte surface (Picker et al, 1991;Erlandsen et al, 1993).…”

“…A further difference between the human E-and L-selectins is that the high-density (but not the low-density) E-selectin cells bound also to the non-sulfated, non-sialylated Le a and Le x pentasaccharides (Larkin et al, 1992). As differences in adhesion to immobilized low-affinity oligosaccharide ligands (Le a and Le x pentasaccharides) have been documented in experiments with the Chinese hamster ovary cells that expressed differing levels of membraneassociated E-selectin (Larkin et al 1992), we suggest that the differences observed here in L-selectin binding to the higher and lower affinity ligands (sulfated and sialyl, respectively) are likely to be manifest in ViVo where the selectin is expressed on the microvilli of leukocyte surface (Picker et al, 1991;Erlandsen et al, 1993). It is known that marked variations occur in the levels of surface expression of the selectin on leukocytes in the process of leukocyte trafficking and infiltration into areas of inflammation: transient increases of L-selectin levels occur under the influence of cytokines such as interferon R and interleukin 2 (Kaldjian & Stoolman, 1995;Palecanda et al, 1992), and diminution of the selectin occurs through shedding in response to stimulation by chemotactic factors and selectin engagement (Griffin et al, 1990;Kishimoto et al, 1989).…”

Anionic phospholipids bind to L-selectin (but not E-selectin) at a site distinct from the carbohydrate-binding site

“…Fucosylated, sialylated oligosaccharides, such as sialyl-Lewis-X [sLex ; NeuAcα2-3,Galβ1-4(α1-3Fuc)GlcNAc], are considered to be minimal ligands for the selectins, although some groups have reported additional ligands for L-or P-selectin that lack sialic acid or fucose. The latter ligands, such as sulphatides, heparins and polyphosphomannan ester, interact with selectins in the presence of EDTA [4][5][6], suggesting that they bind at a site distinct from the classical Ca# + -dependent CRD.…”

Development of fucosyltransferase and fucosidase inhibitors

“…5 In the process of leukocyte recruitment and rolling, sLe x expressed on the surface of leukocytes mediates the recognition toward selectins on the surface of endothelial cells. 6,7 Human fertilization begins when spermatozoa bind to the extracellular matrix of an oocyte. sLe x , the most abundant sugar epitope on the surface of an oocyte, is the major carbohydrate…”