Lewis X and Sialyl Lewis X Glycosphingolipids

Abstract

Lewis X (Le^x) and sialyl Lewis X (sLe^x) are carbohydrate blood group antigens important in cell adhesion. On cell membranes, Le^x and sLe^x may be expressed on glycoproteins or glycosphingolipids (GSLs). The latter are complex macromolecules consisting of an oligosaccharide moiety covalently linked to a ceramide lipid tail. Similar to glycoproteins, Le^x and sLe^x glycans expressed on GSLs can be either simple or multifucosylated, complex, branched, long-chain oligosaccharides. Developmental changes in Le^x and sLe^x GSL expression may play a role in embryonic development and organogenesis. On neutrophils and platelets, sLe^x GSLs may function as the physiologic ligand for endothelial E-selectin, mediating rolling of platelets and neutrophils along activated endothelium. Likewise, endothelial sLe^x GSLs may function as ligands for Lselectin on lymphocytes. In lens, the age-dependent increase in Le^x GSL expression may contribute to cataractogenesis via Le^x-Le^x homotypic adhesion, leading to spatial rearrangement of lens fibers and lens opacification. In malignancy, neoexpression of Le^x and sLe^x GSLs by many tumors may contribute to tumor metastasis via increased adherence to vascular endothelium and platelets. In hematopoietic cells, biosynthesis of Le^x and sLe^x GSLs reflects the action of multiple glycosyltransferases. Lewis^x and sLe^x GSLs may also be chemically synthesized where they have been very useful in structure-function studies of selectin recognition and binding.