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PMID: 19060902 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

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

Nature immunology ·Vol. 10 ·No. 1 ·2009-01-00 ·Pages 101-8

Pruenster M, Mudde L, Bombosi P, Dimitrova S, Zsak M, Middleton J, Richmond A, Graham GJ, Segerer S, Nibbs RJ, Rot A

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.

MeSH Terms
Animals Cell Movement Cells, Cultured Chemokines/metabolism Dogs Duffy Blood-Group System/genetics,metabolism Endothelium, Vascular/immunology,metabolism Humans Leukocytes/immunology Mice Protein Transport Receptors, Cell Surface/genetics,metabolism
Chemicals
ACKR1 protein, human Chemokines Duffy Blood-Group System Receptors, Cell Surface
Authors & Affiliations
11 authors, click to expand affiliations / ORCID
Pruenster Monika
Experimental Pathology, Novartis Institutes for BioMedical Research, Vienna A-1230, Austria.
Mudde Liesbeth
Bombosi Paula
Dimitrova Svetla
Zsak Marion
Middleton Jim
Richmond Ann
Graham Gerard J
Segerer Stephan
Nibbs Robert J B
Rot Antal
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Article Info
Journal
Nature immunology
Abbr.
Nat Immunol
ISSN
1529-2916
DOI
10.1038/ni.1675
Published
2009-01-00
Epub
2008-00-07
Pages
101-8
Language
English
Region
United States
NLM ID
100941354
PMCID
PMC3205989
Subset
IM
Grants
Medical Research Council · G0401634 · United Kingdom
BLRD VA · IK6 BX005225 · United States
NCI NIH HHS · P30 CA068485 · United States
NCI NIH HHS · R01 CA034590 · United States
Corrections
ErratumIn
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External Links
PubMed source DOI: 10.1038/ni.1675 PMC Full Text View journal details
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