Sulfation of L-Selectin Ligands by an HEY-Restricted Sulfotransferase Regulates Lymphocyte Homing to Lymph Nodes

Lymphocytes home to lymph nodes, using L-selectin to bind specific ligands on high endothelial venules (HEV). In vitro studies implicate GlcNAc-6-sulfate as an essential posttranslational modification for ligand activity. Here, we show that genetic deletion of HEC-GlcNAc6ST, a sulfotransferase that...

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Published inImmunity (Cambridge, Mass.) Vol. 15; no. 2; pp. 237 - 247
Main Authors Hemmerich, S, Bistrup, A, Singer, MS, Van Zante, A, Lee, Jin Kyu, Tsay, D, Peters, M, Carminati, J L, Brennan, T J, Carver-Moore, K, Leviten, M, Fuentes, ME, Ruddle, N H, Rosen, S D
Format Journal Article
LanguageEnglish
Published 01.08.2001
Subjects
L-selectin
sulfotransferase
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Summary:Lymphocytes home to lymph nodes, using L-selectin to bind specific ligands on high endothelial venules (HEV). In vitro studies implicate GlcNAc-6-sulfate as an essential posttranslational modification for ligand activity. Here, we show that genetic deletion of HEC-GlcNAc6ST, a sulfotransferase that is highly restricted to HEV, results in the loss of the binding of recombinant L-selectin to the luminal aspect of HEV, elimination of lymphocyte binding in vitro, and markedly reduced in vivo homing. Reactivity with MECA 79, an adhesion-blocking mAb that stains HEV in lymph nodes and vessels in chronic inflammatory sites, is also lost from the luminal aspects of HEV. These results establish a critical role for HEC-GlcNAc6ST in lymphocyte trafficking and suggest it as an important therapeutic target.
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ISSN:1074-7613