CCL19 is a specific ligand of the constitutively recycling atypical human chemokine receptor CRAM-B.
The human chemokine receptor CRAM (chemokine receptor on activated macrophages), encoded by the gene CCRL2, is a new candidate for the atypical chemokine receptor family that includes the receptors DARC, D6 and chemocentryx chemokine receptor (CCX-CKR). CRAM is maturation-stage-dependently expressed on human B lymphocytes and its surface expression is up-regulated upon short-term CCL5 exposure. Here, we demonstrate that the homeostatic chemokine CCL19 is a specific ligand for CRAM. In radioactive labelling studies CCL19 bound to CRAM-expressing cells with an affinity similar to the described binding of its other receptor CCR7. In contrast to the known CCL19/CCR7 ligand/receptor pair, CRAM stimulation by CCL19 did not result in typical chemokine-receptor-dependent cellular activation like calcium mobilization or migration. Instead, we demonstrate that CRAM is constitutively recycling via clathrin-coated pits and able to internalize CCL19 as well as anti-CRAM antibodies. As this absence of classical chemokine receptor responses and the recycling and internalization features are characteristic for non-classical chemokine receptors, we suggest that CRAM is the newest member of this group. As CCL19 is known to be critically involved in lymphocyte and dendritic cell trafficking, CCL19-binding competition by CRAM might be involved in modulating these processes.
Leick
Marion
M
Department of Haematology/Oncology, University Medical Centre, Freiburg, Germany.
Catusse
Julie
J
Follo
Marie
M
Nibbs
Robert J
RJ
Hartmann
Tanja N
TN
Veelken
Hendrik
H
Burger
Meike
M
D002478:Cells, Cultured; D054415:Chemokine CCL19 / Q000378:metabolism*; D006801:Humans; D008024:Ligands; D054388:Receptors, CCR / Q000276:immunology / Q000378:metabolism*
C515460:CCL19 protein, human; C487531:CCRL2 protein, human; D054415:Chemokine CCL19; D008024:Ligands; D054388:Receptors, CCR