title: Endothelial heparan sulfate controls chemokine presentation in recruitment of lymphocytes and dendritic cells to lymph nodes.
abstract: Heparan sulfate can bind several adhesion molecules involved in lymphocyte trafficking. However, the in vivo function of endothelial heparan sulfate in lymphocyte homing and stimulation of the immune response has not been elucidated. Here, we generated mutant mice deficient in the enzyme Ext1, which is required for heparan sulfate synthesis, in a Tek-dependent and inducible manner. Chemokine presentation was diminished in the mutant mice, causing the lack of appropriate integrin-mediated adhesion, and resulted in a marked decrease in lymphocyte sticking to high endothelial venules and in recruitment of resident dendritic cells through lymphatic vessels to the lymph nodes. As a consequence, mutant mice displayed a severe impairment in lymphocyte homing and a compromised contact hypersensitivity response. By contrast, lymphocyte rolling was increased because of loss of electrostatic repulsion by heparan sulfate. These results demonstrate critical roles of endothelial heparan sulfate in immune surveillance and immune response generation.
authors.affiliation: Glycobiology Unit, Sanford-Burnham Medical Research Institute, La Jolla, CA 92037, USA.
authors.forename: Xingfeng
authors.initials: X
authors.lastname: Bao
authors.forename: E Ashley
authors.initials: EA
authors.lastname: Moseman
authors.forename: Hideo
authors.initials: H
authors.lastname: Saito
authors.forename: Bronislawa
authors.initials: B
authors.lastname: Petryniak
authors.forename: Bronislawa
authors.initials: B
authors.lastname: Petryanik
authors.forename: Aude
authors.initials: A
authors.lastname: Thiriot
authors.forename: Shingo
authors.initials: S
authors.lastname: Hatakeyama
authors.forename: Yuki
authors.initials: Y
authors.lastname: Ito
authors.forename: Hiroto
authors.initials: H
authors.lastname: Kawashima
authors.forename: Yu
authors.initials: Y
authors.lastname: Yamaguchi
authors.forename: John B
authors.initials: JB
authors.lastname: Lowe
authors.forename: Ulrich H
authors.initials: UH
authors.lastname: von Andrian
authors.forename: Minoru
authors.initials: M
authors.lastname: Fukuda
mesh_terms: D000818:Animals; D002448:Cell Adhesion / Q000276:immunology; D018925:Chemokines / Q000276:immunology* / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D004730:Endothelium, Vascular / Q000276:immunology; D006497:Heparan Sulfate / Q000276:immunology* / Q000378:metabolism; D016023:Integrins / Q000276:immunology; D008198:Lymph Nodes / Q000276:immunology* / Q000378:metabolism; D008214:Lymphocytes / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D017351:N-Acetylglucosaminyltransferases / Q000172:deficiency; D014699:Venules / Q000276:immunology / Q000378:metabolism; D000099058:Exostosin 1
chemical_list: D018925:Chemokines; D006497:Heparan Sulfate; D016023:Integrins; D017351:N-Acetylglucosaminyltransferases; D000099058:Exostosin 1