lewis-x-antigen and Dermatitis--Contact

Lymphocyte homing is mediated by specific interaction between L-selectin on lymphocytes and the carbohydrate ligand 6-sulfo sialyl Lewis X on high endothelial venules. Here we generated mice lacking both core 1 extension and core 2 branching enzymes to assess the functions of O-glycan-borne L-selectin ligands in vivo. Mutant mice maintained robust lymphocyte homing, yet they lacked O-glycan L-selectin ligands. Biochemical analyses identified a class of N-glycans bearing the 6-sulfo sialyl Lewis X L-selectin ligand in high endothelial venules. These N-glycans supported the binding of L-selectin to high endothelial venules in vitro and contributed in vivo to O-glycan-independent lymphocyte homing in wild-type and mutant mice. Our results demonstrate the critical function of N-glycan-linked 6-sulfo sialyl Lewis X in L-selectin-dependent lymphocyte homing and recruitment.

Topics: Animals; Antigens, Surface; Cell Adhesion; Dermatitis, Contact; Endothelium, Lymphatic; L-Selectin; Lewis X Antigen; Lymph Nodes; Lymphocytes; Membrane Proteins; Mice; Mice, Knockout; Microscopy, Fluorescence; Oligosaccharides; Polysaccharides; Sialyl Lewis X Antigen

Lymphocyte homing is mediated by specific interactions between L-selectin on lymphocytes and sulfated carbohydrates restricted to high endothelial venules in lymph nodes. Here we generated mice deficient in both N-acetylglucosamine-6-O-sulfotransferase 1 (GlcNAc6ST-1) and GlcNAc6ST-2 and found that mutant mice had approximately 75% less homing of lymphocytes to the peripheral lymph nodes than did wild-type mice. Consequently, these mice had lower contact hypersensitivity responses than those of wild-type mice. Carbohydrate structural analysis showed that 6-sulfo sialyl Lewis X, a dominant ligand for L-selectin, was almost completely absent from the high endothelial venules of these mutant mice, whereas the amount of unsulfated sialyl Lewis X was much greater. These results demonstrate the essential function of GlcNAc6ST-1 and GlcNAc6ST-2 in L-selectin ligand biosynthesis in high endothelial venules and their importance in immune surveillance.

Topics: Animals; Carbohydrate Conformation; Carbohydrate Sequence; Carbohydrate Sulfotransferases; Cell Movement; Dermatitis, Contact; Endothelium, Lymphatic; L-Selectin; Leukocyte Rolling; Lewis X Antigen; Ligands; Lymph Nodes; Lymphocytes; Mice; Mice, Knockout; Mucins; Mutation; Oligosaccharides; Sialyl Lewis X Antigen; Substrate Specificity; Sulfotransferases