Abstract:
: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 beta2 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.
journal_name
Biol Pharm Bulljournal_title
Biological & pharmaceutical bulletinauthors
Kawashima Hdoi
10.1248/bpb.29.2343subject
Has Abstractpub_date
2006-12-01 00:00:00pages
2343-9issue
12eissn
0918-6158issn
1347-5215pii
JST.JSTAGE/bpb/29.2343journal_volume
29pub_type
杂志文章,评审abstract::The mechanistic/mammalian target of rapamycin complex-1 (mTORC1) integrates multiple signaling pathways and regulates various cellular processes. Tuberous sclerosis complex 1 (Tsc1) and complex 2 (Tsc2) are critical negative regulators of mTORC1. Mouse genetic studies, including ours, have revealed that inactivation o...
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pub_type: 杂志文章
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pub_type: 杂志文章
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更新日期:2004-10-01 00:00:00
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更新日期:2002-06-01 00:00:00
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journal_title:Biological & pharmaceutical bulletin
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journal_title:Biological & pharmaceutical bulletin
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journal_title:Biological & pharmaceutical bulletin
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journal_title:Biological & pharmaceutical bulletin
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journal_title:Biological & pharmaceutical bulletin
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