CCL19 is a specific ligand of the constitutively recycling atypical human chemokine receptor CRAM-B

Leick, M., Catusse, J., Follo, M., Nibbs, R.J. , Hartmann, T.N., Veelken, H. and Burger, M. (2010) CCL19 is a specific ligand of the constitutively recycling atypical human chemokine receptor CRAM-B. Immunology, 129(4), pp. 536-546. (doi: 10.1111/j.1365-2567.2009.03209.x)

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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.

Item Type:Articles
Glasgow Author(s) Enlighten ID:Nibbs, Professor Rob
Authors: Leick, M., Catusse, J., Follo, M., Nibbs, R.J., Hartmann, T.N., Veelken, H., and Burger, M.
Subjects:R Medicine > R Medicine (General)
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Immunology
ISSN (Online):1365-2567
Published Online:02 December 2009

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