title: Critical functions of N-glycans in L-selectin-mediated lymphocyte homing and recruitment.
abstract: 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.
authors.affiliation: Glycobiology Program, Cancer Research Center, Burnham Institute for Medical Research, La Jolla, California 92037, USA.
authors.forename: Junya
authors.initials: J
authors.lastname: Mitoma
authors.forename: Xingfeng
authors.initials: X
authors.lastname: Bao
authors.forename: Bronislawa
authors.initials: B
authors.lastname: Petryanik
authors.forename: Patrick
authors.initials: P
authors.lastname: Schaerli
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Gauguet
authors.forename: Shin-Yi
authors.initials: SY
authors.lastname: Yu
authors.forename: Hiroto
authors.initials: H
authors.lastname: Kawashima
authors.forename: Hideo
authors.initials: H
authors.lastname: Saito
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Ohtsubo
authors.forename: Jamey D
authors.initials: JD
authors.lastname: Marth
authors.forename: Kay-Hooi
authors.initials: KH
authors.lastname: Khoo
authors.forename: Ulrich H
authors.initials: UH
authors.lastname: von Andrian
authors.forename: John B
authors.initials: JB
authors.lastname: Lowe
authors.forename: Minoru
authors.initials: M
authors.lastname: Fukuda
mesh_terms: D000818:Animals; D000954:Antigens, Surface / Q000276:immunology; D002448:Cell Adhesion / Q000276:immunology; D003877:Dermatitis, Contact / Q000276:immunology; D004729:Endothelium, Lymphatic / Q000166:cytology / Q000276:immunology; D019041:L-Selectin / Q000276:immunology*; D016256:Lewis X Antigen / Q000031:analogs & derivatives; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology*; D008214:Lymphocytes / Q000166:cytology / Q000276:immunology*; D008565:Membrane Proteins / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D008856:Microscopy, Fluorescence; D009844:Oligosaccharides / Q000276:immunology*; D011134:Polysaccharides / Q000276:immunology*; D000080506:Sialyl Lewis X Antigen / Q000031:analogs & derivatives
chemical_list: C086949:6'-sulfated sialyl Lewis x; D000954:Antigens, Surface; C069886:L-selectin counter-receptors; D016256:Lewis X Antigen; D008565:Membrane Proteins; D009844:Oligosaccharides; D011134:Polysaccharides; D000080506:Sialyl Lewis X Antigen; D019041:L-Selectin