Roles of Sulfated Glycans in Lymphocyte Homing

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概要

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• Lymphocyte homing is mediated by a specific interaction between the lymphocyte homing receptor L-selectin and its sulfated glycoprotein ligands, which are expressed on high endothelial venules (HEV) in the lymph nodes. To examine the significance of the sulfation of L-selectin ligands, our group has generated gene-targeted mice deficient in both N-acetylglucosamine-6-O-sulfotransferase (GlcNAc6ST)-1 and GlcNAc6ST-2. The mutant mice show approximately 75% less lymphocyte homing to the peripheral lymph nodes than normal, indicating that GlcNAc6ST-1 and GlcNAc6ST-2 play a major role in the biosynthesis of L-selectin ligand in HEV. In agreement with this interpretation, an oligosaccharide analysis indicated that 6-sulfo sialyl Lewis X, a major L-selectin ligand sulfated glycan, is almost completely abrogated in the double-deficient mice. Lymphocyte homing into the parenchyma of lymph nodes is mediated by a series of interactions: rolling, activation by chemokines, integrin-mediated adhesion, and transmigration. During the rolling interaction, which is mediated by L-selectin and sulfated glycans, lymphocytes receive activation signals from chemokines presented on the surface of HEV by heparan sulfate, a sulfated glycosaminoglycan, which leads to the activation of lymphocyte β2 integrin. Sulfated glycans are thus involved in both the rolling and the chemokine-induced activation steps between lymphocytes and HEV. In this article, recent findings on the roles of sulfated glycans in both of these lymphocyte-homing steps will be reviewed. The possible application of sulfated glycans for the prevention of inflammatory disorders will also be discussed.

• 公益社団法人日本薬学会の論文
• 2006-12-01

著者

• KAWASHIMA Hiroto

  Department of Bioregulation, Biomedical Research Center, Osaka University Medical School

• Kawashima Hiroto

  Department Of Bioregulation Biomedical Research Center Osaka University Graduate School Of Medicine

• Kawashima Hiroto

  Department Of Microbiology School Of Pharmaceutical Sciences University Of Shizuoka

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• Identification and characterization of ligands for L-selectin in the kidney. I. Versican, a large chondroitin sulfate proteoglycan, is a ligand for L-selectin
• Roles of Sulfated Glycans in Lymphocyte Homing
• A functional epitope on P-selectin that srpports binding of P-selectin to P-selectin glycoprotein ligand-1 but not to sialyl Lewis X oligosacharides
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• Identification and Characterization of Ligands for L-Selectin in the Kidney. III. Characterization of L-Selectin Reactive Heparan Sulfate Proteoglycansl.

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