Cutting edge: scavenging of inflammatory CC chemokines by the promiscuous putatively silent chemokine receptor D6.
In an effort to define the actual function of the promiscuous putatively silent chemokine receptor D6, transfectants were generated in different cell types. Engagement of D6 by inflammatory CC chemokines elicited no calcium response nor chemotaxis, but resulted in efficient agonist internalization and degradation. Also in lymphatic endothelium, where this receptor is expressed in vivo, D6 did not elicit cellular responses other than ligand internalization and degradation. In particular, no evidence was obtained for D6-mediated transcytosis of chemokines in the apical-to-basal or basal-to-apical directions. These results indicate that D6 acts as an inflammatory chemokine scavenging nonactivatory decoy receptors and suggest that in lymphatic vessels D6 may function as a gatekeeper for inflammatory CC chemokines, by clearing them and preventing excessive diffusion via afferent lymphatics to lymph nodes.
Fra
Anna M
AM
Section of General Pathology and Immunology, Department of Biomedical Sciences and Biotechnology, University of Brescia, Brescia, Italy.
Locati
Massimo
M
Otero
Karel
K
Sironi
Marina
M
Signorelli
Paola
P
Massardi
Maria L
ML
Gobbi
Marco
M
Vecchi
Annunciata
A
Sozzani
Silvano
S
Mantovani
Alberto
A
D000818:Animals; D016466:CHO Cells; D002478:Cells, Cultured; D019742:Chemokines, CC / Q000378:metabolism*; D006224:Cricetinae; D004729:Endothelium, Lymphatic / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000276:immunology / Q000378:metabolism; D007457:Iodine Radioisotopes / Q000378:metabolism; D008024:Ligands; D051379:Mice; D008811:Mice, Inbred DBA; D011485:Protein Binding / Q000276:immunology; D011869:Radioligand Assay; D054447:Receptors, CCR10; D019707:Receptors, Chemokine / Q000096:biosynthesis / Q000502:physiology*; D015398:Signal Transduction / Q000276:immunology; D014162:Transfection; D014407:Tumor Cells, Cultured; D000097628:Chemokine Receptor D6
D019742:Chemokines, CC; D007457:Iodine Radioisotopes; D008024:Ligands; D054447:Receptors, CCR10; D019707:Receptors, Chemokine; D000097628:Chemokine Receptor D6