Regulatory roles of carbohydrate ligands for selectins in the homing of lymphocytes

Cell surface carbohydrate determinants figure heavily in the regulation of lymphocyte homing and the inflammatory recruitment of leukocytes. The recently described sulfated carbohydrate ligand for selectins, sialyl 6-sulfo Lewis x, is mainly involved in the routine homing of various subsets of lymphocytes, such as naı̈ve helper T cells, and skin- and gut-homing helper memory T cells. The homing of lymphocytes is regulated by a unique post-translational modification of sialic acid moieties that occurs specifically in sulfated selectin ligands, whereby the sialic acid loses its N-acetyl group and is converted into a 1-5 cyclic derivative. By contrast, nonsulfated carbohydrate ligands of the selectins, such as sialyl Lewis x, are mainly involved in the recruitment of leukocytes during inflammation. The increment of sialyl Lewis x expression upon inflammatory stimuli is mediated by transcriptional induction of fucosyltransferase genes. Sialyl 6-sulfo Lewis x is a selectin ligand in the routine process of site-specific homing of various subsets of T cells, whereas sialyl Lewis x is an emergency ligand for selectins that preferentially operate under inflammatory conditions.