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The Duffy antigen receptor for chemokines transports chemokines and supports their promigratory activity


Pruenster, M; Mudde, L; Bombosi, P; Dimitrova, S; Zsak, M; Middleton, J; Richmond, A; Graham, G; Segerer, S; Nibbs, R; Rot, A (2009). The Duffy antigen receptor for chemokines transports chemokines and supports their promigratory activity. Nature Immunology, 10(1):101-108.

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.

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.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Clinic for Nephrology
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:2009
Deposited On:07 Apr 2009 09:23
Last Modified:05 Apr 2016 13:02
Publisher:Nature Publishing Group
ISSN:1529-2908
Additional Information:PDF mit Erratum vom 2009 Feb;10(2):223 / © 2009 Nature Publishing Group - Full text at http://www.nature.com/ni/journal/v10/n1/full/ni.1675.html
Publisher DOI:https://doi.org/10.1038/ni.1675
Related URLs:http://www.nature.com/ni/journal/v10/n1/full/ni.1675.html (Publisher)
PubMed ID:19060902

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