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M311150200v1
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Papers In Press, published online ahead of print October 30, 2003
J. Biol. Chem, 10.1074/jbc.M311150200
Submitted on October 10, 2003
Revised on October 28, 2003
Accepted on October 30, 2003

Core 2 branching ß1,6-N-acetylglucosaminyl transferase and high endothelial venule-restricted sulfotransferase collaboratively control lymphocyte homing

Nobuyoshi Hiraoka, Hiroto Kawashima, Bronislawa Petryniak, Jun Nakayama, Junya Mitoma, Jamey D. Marth, John B. Lowe, and Minoru Fukuda

Glycobiology Program, The Burnham Institute, La Jolla, CA 92037

Corresponding Author: minoru{at}burnham.org

L-selectin mediates lymphocyte homing by facilitating lymphocyte adhesion to carbohydrate ligands expressed on high endothelial venules (HEV) of the secondary lymphoid organs. Previous studies demonstrated that L-selectin ligand sulfotransferase (LSST) forms 6-sulfo sialyl Lewis x (sLex) on both core 2 branch and MECA-79 positive extended core 1 O-glycans, but the chemical nature and roles of HEV ligands elaborated by LSST and core2 ß1,6-N-acetyglucosaminyltransferase-1 (Core2GlcNAcT) have been undefined. In the present study, we have generated mutant mice with deficient LSST and show that inactivation of LSST gene alone leads to only partial impairment of lymphocyte homing to peripheral lymph nodes, and moderate reduction in lymphocyte counts in the peripheral lymph nodes, despite the fact that L-selectin ligands that contain 6-sulfo sLex are reduced at HEV. By contrast, LSST/Core2GlcNAcT double null mice exhibited a markedly reduced lymphocyte homing and reduced lymphocyte counts as a result of significantly decreased 6-sulfo sLex on HEV L-selectin counterreceptors, relative to LSST- or Core2GlcNAcT- single null mice. Moreover, induction of LSST and Core2GlcNAcT transcripts was observed in HEV-like structure formed in the salivary gland of non-obese diabetic mouse, which displays chronic inflammation. These results indicate that LSST and Core2GlcNAcT cooperatively synthesize HEV-specific L-selectin ligands required for lymphocyte homing and suggest that LSST and Core2GlcNAcT play a critical role in lymphocyte trafficking during chronic inflammation.


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