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Published online before print February 15, 2005

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(Journal of Leukocyte Biology. 2005;77:739-747.)
© 2005 by Society for Leukocyte Biology

Novel monoclonal antibodies detect elevated levels of the chemokine CCL18/DC-CK1 in serum and body fluids in pathological conditions

Robbert van der Voort^*, Matthijs Kramer^*, Ernst Lindhout^*,1, Ruurd Torensma^*, Dagmar Eleveld^*, Antoine W. T. van Lieshout, Maaike Looman^*, Theo Ruers, Timothy R. D. J. Radstake, Carl G. Figdor^* and Gosse J. Adema^*,2

^* Department of Tumor Immunology, Nijmegen Center for Molecular Life Sciences, and
Rheumatology and
Surgical Oncology, University Medical Center St Radboud, Nijmegen, The Netherlands

² Correspondence: Department of Tumor Immunology, NCMLS, University Medical Center St Radboud, Nijmegen, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands. E-mail: g.adema{at}ncmls.kun.nl

CC chemokine ligand 18/dendritic cell-chemokine 1 (CCL18/DC-CK1) is a CC chemokine, preferentially expressed by DC, which acts as a chemoattractant for naive T cells and mantle zone B cells. Applying a newly developed CCL18/DC-CK1 sandwich enzyme-linked immunosorbent assay, we demonstrate that DC secrete high amounts of CCL18/DC-CK1 and that this expression can be increased by interleukin-10. High levels of CCL18/DC-CK1 were also detected in human serum (average of 88 ng/ml). Moreover, elevated CCL18/DC-CK1 levels were detected in synovial fluid from rheumatoid arthritis patients and in drain fluid (average of 254 ng/ml and 122 ng/ml, respectively). Immunoprecipitation experiment using anti-CCL18/DC-CK1 monoclonal antibodies revealed a protein of 6–7 kDa in serum and drain fluid that was indistinguishable from recombinant CCL18/DC-CK1 on Western blot and in re-aggregation assays. The concentration of CCL18/DC-CK1 found in human serum is in the same order of magnitude as was previously reported to completely inhibit CCL11/eotaxin-induced CC chemokine receptor 3 (CCR3) activation and consequent migration of eosinophils. CCL18/DC-CK1 may therefore function as an agonist (for naive T and B cells) and as an antagonist for CCR3-expressing leukocytes such as eosinophils.

Key Words: human • dendritic cells • cell trafficking • inflammation

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