title: Sulfation of L-selectin ligands by an HEV-restricted sulfotransferase regulates lymphocyte homing to lymph nodes.
abstract: 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.
authors.affiliation: Department of Respiratory Diseases, Roche Bioscience, 3401 Hillview Avenue, Palo Alto, CA 94304, USA. sdr@itsa.ucsf.edu
authors.forename: S
authors.initials: S
authors.lastname: Hemmerich
authors.forename: A
authors.initials: A
authors.lastname: Bistrup
authors.forename: M S
authors.initials: MS
authors.lastname: Singer
authors.forename: A
authors.initials: A
authors.lastname: van Zante
authors.forename: J K
authors.initials: JK
authors.lastname: Lee
authors.forename: D
authors.initials: D
authors.lastname: Tsay
authors.forename: M
authors.initials: M
authors.lastname: Peters
authors.forename: J L
authors.initials: JL
authors.lastname: Carminati
authors.forename: T J
authors.initials: TJ
authors.lastname: Brennan
authors.forename: K
authors.initials: K
authors.lastname: Carver-Moore
authors.forename: M
authors.initials: M
authors.lastname: Leviten
authors.forename: M E
authors.initials: ME
authors.lastname: Fuentes
authors.forename: N H
authors.initials: NH
authors.lastname: Ruddle
authors.forename: S D
authors.initials: SD
authors.lastname: Rosen
mesh_terms: D000818:Animals; D002448:Cell Adhesion; D002634:Chemotaxis, Leukocyte; D019041:L-Selectin / Q000378:metabolism*; D037102:Lectins / Q000378:metabolism; D008024:Ligands; D008198:Lymph Nodes / Q000166:cytology*; D008208:Lymphatic System / Q000201:enzymology*; D008214:Lymphocytes / Q000166:cytology*; D051379:Mice; D008817:Mice, Mutant Strains; D015238:Sulfotransferases / Q000235:genetics / Q000378:metabolism*
chemical_list: D037102:Lectins; D008024:Ligands; D019041:L-Selectin; D015238:Sulfotransferases