Article abstract
Nature Immunology 10, 101 - 108 (2008)
Published online: 7 December 2008 | Corrected online: 16 January 2009 | doi:10.1038/ni.1675
There is an Erratum (February 2009) associated with this Article.
The Duffy antigen receptor for chemokines transports chemokines and supports their promigratory activity
Monika Pruenster1, Liesbeth Mudde1, Paula Bombosi1, Svetla Dimitrova1, Marion Zsak1, Jim Middleton1,2, Ann Richmond3, Gerard J Graham4, Stephan Segerer5,6, Robert J B Nibbs4 & Antal Rot1
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.
- Experimental Pathology, Novartis Institutes for BioMedical Research, Vienna A-1230, Austria.
- Medical School, Keele University, Robert Jones & Agnes Hunt Orthopaedic Hospital, Oswestry SY10 7AG, UK.
- Department of Veterans Affairs and Department of Cell Biology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA.
- Division of Immunology, Infection and Inflammation, Glasgow Biomedical Research Centre, University of Glasgow, Glasgow G12 8TA, UK.
- Medizinische Poliklinik, University of Munich, Munich D-80337, Germany.
- Clinic for Nephrology, University of Zurich, Zurich CH-8091, Switzerland.
Correspondence to: Antal Rot1 e-mail: antal@gmx.net
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