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, Gosse J Adema

Research output: Contribution to journalArticleAcademicpeer-review

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.

Original languageEnglish
Pages (from-to)739-47
Number of pages9
JournalJournal of Leukocyte Biology
Volume77
Issue number5
DOIs
Publication statusPublished - 2005
Externally publishedYes

Keywords

  • Antibodies, Monoclonal
  • Antibody Specificity
  • Arthritis, Rheumatoid
  • Body Fluids
  • Cells, Cultured
  • Chemokines, CC
  • Chemotaxis, Leukocyte
  • Dendritic Cells
  • Enzyme-Linked Immunosorbent Assay
  • Humans
  • Interleukin-10
  • Leukocytes
  • Receptors, CCR3
  • Receptors, Chemokine
  • Recombinant Proteins
  • Journal Article
  • Research Support, Non-U.S. Gov't

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