title: CCL19 is a specific ligand of the constitutively recycling atypical human chemokine receptor CRAM-B.
abstract: 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.
authors.affiliation: Department of Haematology/Oncology, University Medical Centre, Freiburg, Germany.
authors.forename: Marion
authors.initials: M
authors.lastname: Leick
authors.forename: Julie
authors.initials: J
authors.lastname: Catusse
authors.forename: Marie
authors.initials: M
authors.lastname: Follo
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Nibbs
authors.forename: Tanja N
authors.initials: TN
authors.lastname: Hartmann
authors.forename: Hendrik
authors.initials: H
authors.lastname: Veelken
authors.forename: Meike
authors.initials: M
authors.lastname: Burger
mesh_terms: D002478:Cells, Cultured; D054415:Chemokine CCL19 / Q000378:metabolism*; D006801:Humans; D008024:Ligands; D054388:Receptors, CCR / Q000276:immunology / Q000378:metabolism*
chemical_list: C515460:CCL19 protein, human; C487531:CCRL2 protein, human; D054415:Chemokine CCL19; D008024:Ligands; D054388:Receptors, CCR