Contribution of Duffy antigen to chemokine function.
In addition to classical G protein-coupled receptors (GPCRs), a group of alternative, "silent" chemokine receptors has recently been identified. These serpentine molecules are not coupled to G proteins and subsequent signaling cascades, but can efficiently internalize their cognate chemokine ligands, thus act as "interceptors" (internalizing receptors). Here we discuss a mechanism by which a member of this family, Duffy antigen (DARC), contributes to chemokine-induced leukocyte emigration. Cumulative experimental evidence suggests that DARC on venular endothelium mediates chemokine internalization at the abluminal surface followed by transcytosis and transfer of the chemokine cargo onto the luminal surface. DARC is also expressed on the erythrocyte surface of DARC positive individuals. Erythrocyte DARC binds plasma chemokines which results, on one hand, in impediment of the chemokines loss from the circulation and, on the other hand, in neutralization of chemokines in the blood. This leads to leukocyte protection from inadvertent "desensitization" and enhancement of leukocyte recruitment.
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Antal
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Novartis Institutes for BioMedical Research, Brunnerstrasse 59, A-1230 Vienna, Austria. antal.rot@novartis.com
D000818:Animals; D018925:Chemokines / Q000502:physiology*; D004375:Duffy Blood-Group System / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D004727:Endothelium / Q000737:chemistry / Q000276:immunology; D004912:Erythrocytes / Q000737:chemistry / Q000276:immunology; D006801:Humans; D011956:Receptors, Cell Surface / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D019707:Receptors, Chemokine / Q000502:physiology*
C473745:ACKR1 protein, human; D018925:Chemokines; D004375:Duffy Blood-Group System; D011956:Receptors, Cell Surface; D019707:Receptors, Chemokine