Lewis X and sialyl Lewis X glycosphingolipids

Abstract

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