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CCL19 is a specific ligand of the constitutively recycling atypical human chemokine receptor CRAM‐B
Author(s) -
Leick Marion,
Catusse Julie,
Follo Marie,
Nibbs Robert J.,
Hartmann Tanja N.,
Veelken Hendrik,
Burger Meike
Publication year - 2010
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/j.1365-2567.2009.03209.x
Subject(s) - ccl19 , ccr1 , c c chemokine receptor type 7 , chemokine receptor , ccl21 , c c chemokine receptor type 6 , ccl25 , microbiology and biotechnology , chemokine receptor ccr5 , xcl2 , cc chemokine receptors , ccl13 , ccl5 , biology , chemistry , chemokine , receptor , immunology , t cell , biochemistry , immune system , il 2 receptor
Summary 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.