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 GJ, Segerer S, Nibbs RJ, Rot A
Nat Immunol. 2009 10 (1): 101-8

PMID: 19060902 · PMCID: PMC3205989 · DOI:10.1038/ni.1675

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 (12)

Animals Cell Movement Cells, Cultured Chemokines Dogs Duffy Blood-Group System Endothelium, Vascular Humans Leukocytes Mice Protein Transport Receptors, Cell Surface

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