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Published online before print February 15, 2005

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© by The Society for Leukocyte Biology
Journal of Leukocyte Biology, doi:10.1189/jlb.0804435

Received for publication August 2, 2004.
Revised January 20, 2005.
Accepted for publication January 24, 2005.

Article

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 ^*, 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 ^*@

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

^@ To whom correspondence should be addressed. E-mail: g.adema{at}ncmls.kun.nl.

	Abstract

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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