Nature Immunology 6, 1105 - 1113 (2005)
Published online: 9 October 2005; | doi:10.1038/ni1258
A major class of L-selectin ligands is eliminated in mice deficient in two sulfotransferases expressed in high endothelial venulesKenji Uchimura1, Jean-Marc Gauguet2, Mark S Singer1, Durwin Tsay1, Reiji Kannagi3, Takashi Muramatsu4, Ulrich H von Andrian2
& Steven D Rosen11
Department of Anatomy, Program in Immunology, Cardiovascular Research Institute, University of California, San Francisco, California 94143, USA. 2
The CBR Institute for Biomedical Research and Department of Pathology, Harvard Medical School, Boston, Massachusetts, 02115, USA. 3
Program of Molecular Pathology, Aichi Cancer Center, Research Institute, Nagoya 464-8681, Japan. 4
Department of Biochemistry, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan.
Correspondence should be addressed to Steven D Rosen sdr@itsa.ucsf.edu The interaction of L-selectin on lymphocytes with sulfated ligands on high endothelial venules leads to rolling and is critical for recruitment of lymphocytes into peripheral lymph nodes. Peripheral node addressin represents a class of L-selectin ligands recognized by the function-blocking monoclonal antibody MECA-79. Its epitope overlaps with sialyl 6-sulfo Lewis X, an L-selectin recognition determinant. Here, mice lacking two N-acetylglucosamine-6-O-sulfotransferases (GlcNAc6ST-1 and GlcNAc6ST-2) demonstrated elimination of both peripheral node addressin and sialyl 6-sulfo Lewis X in high endothelial venules, considerably reduced lymphocyte homing to peripheral lymph nodes and reduced sticking of lymphocytes along high endothelial venules. Our results establish an essential function for the sulfotransferases in L-selectin ligand synthesis and may have relevance for therapy of inflammatory diseases.
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