Article abstract
Nature Immunology 8, 409 - 418 (2007)
Published online: 4 March 2007 | doi:10.1038/ni1442
Critical functions of N-glycans in L-selectin-mediated lymphocyte homing and recruitment
Junya Mitoma1,6,7, Xingfeng Bao1,7, Bronislawa Petryanik2, Patrick Schaerli3, Jean-Marc Gauguet3, Shin-Yi Yu4, Hiroto Kawashima1, Hideo Saito1, Kazuaki Ohtsubo5, Jamey D Marth5, Kay-Hooi Khoo4, Ulrich H von Andrian3, John B Lowe2 & Minoru Fukuda1
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.
- Glycobiology Program, Cancer Research Center, Burnham Institute for Medical Research, La Jolla, California 92037, USA.
- Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106, USA.
- CBR Institute for Biomedical Research and Department of Pathology, Harvard Medical School, Boston, Massachusetts 02115, USA.
- Institute of Biological Chemistry, Academia Sinica, Taipei 11529, Taiwan.
- Howard Hughes Medical Institute and Department of Cellular and Molecular Medicine, University of California San Diego, La Jolla, California 92093, USA.
- Present address: Division of Glyco-Signal Research, Institute of Molecular Biomembrane and Glycobiology, Tohoku Pharmaceutical University, 4-4-1 Komatsushima, Aoba, Sendai, Miyagi 981-8558, Japan.
- These authors equally contributed to this work.
Correspondence to: Minoru Fukuda1 e-mail: minoru@burnham.org
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