title: Plasmacytoid dendritic cells employ multiple cell adhesion molecules sequentially to interact with high endothelial venule cells--molecular basis of their trafficking to lymph nodes.
abstract: Plasmacytoid dendritic cells (pDCs) are natural type I IFN-producing cells found in lymphoid tissues, where they support both innate and adaptive immune responses. They emigrate from the blood to lymph nodes, apparently through high endothelial venules (HEVs), but little is known about the mechanism. We have investigated the molecular mechanisms of pDC migration using freshly isolated DCs and HEV cells. We found that pDCs bound avidly to HEV cells and then transmigrated underneath them. Two observations suggested that these binding and migration steps are differentially regulated. First, treatment of pDCs with pertussis toxin blocked transmigration but not binding. Second, pDCs were able to bind but not to transmigrate under non-HEV endothelial cells, although the binding was observed to both HEV and non-HEV endothelial cells. Antibody inhibition studies indicated that the binding process was mediated by alphaL and alpha4 integrins on pDCs and by intercellular adhesion molecule (ICAM)-1, ICAM-2 and vascular cell adhesion molecule-1 on HEVs. The transmigration process was also mediated by alphaL and alpha4 integrins on pDCs, with junctional adhesion molecule-A on HEV cells apparently serving as an additional ligand for alphaL integrin. These data show for the first time that pDCs employ multiple adhesion molecules sequentially in the processes of adhesion to and transmigration through HEVs.
authors.affiliation: Laboratory of Immunodynamics, Department of Microbiology and Immunology, Osaka University Graduate School of Medicine, Suita 565-0871, Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Matsutani
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Tanaka
authors.forename: Kazuo
authors.initials: K
authors.lastname: Tohya
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Otani
authors.forename: Myoung Ho
authors.initials: MH
authors.lastname: Jang
authors.forename: Eiji
authors.initials: E
authors.lastname: Umemoto
authors.forename: Kanako
authors.initials: K
authors.lastname: Taniguchi
authors.forename: Haruko
authors.initials: H
authors.lastname: Hayasaka
authors.forename: Koichi
authors.initials: K
authors.lastname: Ueda
authors.forename: Masayuki
authors.initials: M
authors.lastname: Miyasaka
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001665:Binding Sites; D002448:Cell Adhesion / Q000276:immunology; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002465:Cell Movement / Q000187:drug effects / Q000276:immunology; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D042783:Endothelial Cells / Q000187:drug effects / Q000276:immunology*; D004729:Endothelium, Lymphatic / Q000166:cytology / Q000276:immunology*; D008198:Lymph Nodes / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D037342:Pertussis Toxin / Q000494:pharmacology; D014699:Venules / Q000166:cytology / Q000276:immunology*