title: The Duffy antigen receptor for chemokines transports chemokines and supports their promigratory activity.
abstract: The Duffy antigen receptor for chemokines (DARC) belongs to a family of 'silent' heptahelical chemokine receptors that do not couple to G proteins and fail to transmit measurable intracellular signals. DARC binds most inflammatory chemokines and is prominently expressed on venular endothelial cells, where its function has remained contentious. Here we show that DARC, like other silent receptors, internalized chemokines but did not effectively scavenge them. Instead, DARC mediated chemokine transcytosis, which led to apical retention of intact chemokines and more leukocyte migration across monolayers expressing DARC. Mice overexpressing DARC on blood vessel endothelium had enhanced chemokine-induced leukocyte extravasation and contact-hypersensitivity reactions. Thus, interactions of chemokines with DARC support their activity on apposing leukocytes in vitro and in vivo.
authors.affiliation: Experimental Pathology, Novartis Institutes for BioMedical Research, Vienna A-1230, Austria.
authors.forename: Monika
authors.initials: M
authors.lastname: Pruenster
authors.forename: Liesbeth
authors.initials: L
authors.lastname: Mudde
authors.forename: Paula
authors.initials: P
authors.lastname: Bombosi
authors.forename: Svetla
authors.initials: S
authors.lastname: Dimitrova
authors.forename: Marion
authors.initials: M
authors.lastname: Zsak
authors.forename: Jim
authors.initials: J
authors.lastname: Middleton
authors.forename: Ann
authors.initials: A
authors.lastname: Richmond
authors.forename: Gerard J
authors.initials: GJ
authors.lastname: Graham
authors.forename: Stephan
authors.initials: S
authors.lastname: Segerer
authors.forename: Robert J B
authors.initials: RJ
authors.lastname: Nibbs
authors.forename: Antal
authors.initials: A
authors.lastname: Rot
mesh_terms: D000818:Animals; D002465:Cell Movement; D002478:Cells, Cultured; D018925:Chemokines / Q000378:metabolism*; D004285:Dogs; D004375:Duffy Blood-Group System / Q000235:genetics / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007962:Leukocytes / Q000276:immunology*; D051379:Mice; D021381:Protein Transport; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*
chemical_list: C473745:ACKR1 protein, human; D018925:Chemokines; D004375:Duffy Blood-Group System; D011956:Receptors, Cell Surface