Novel monoclonal antibodies detect elevated levels of the chemokine CCL18/DC-CK1 in serum and body fluids in pathological conditions.
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.
van der Voort
Robbert
R
Department of Tumor Immunology, Nijmegen Center for Molecular Life Scences, University Medical Center St Radboud, Nijmegen, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands.
Kramer
Matthijs
M
Lindhout
Ernst
E
Torensma
Ruurd
R
Eleveld
Dagmar
D
van Lieshout
Antoine W T
AW
Looman
Maaike
M
Ruers
Theo
T
Radstake
Timothy R D J
TR
Figdor
Carl G
CG
Adema
Gosse J
GJ
D000911:Antibodies, Monoclonal / Q000276:immunology*; D000918:Antibody Specificity; D001172:Arthritis, Rheumatoid / Q000276:immunology*; D001826:Body Fluids / Q000276:immunology; D002478:Cells, Cultured; D019742:Chemokines, CC / Q000097:blood / Q000276:immunology* / Q000378:metabolism; D002634:Chemotaxis, Leukocyte / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D016753:Interleukin-10 / Q000276:immunology*; D007962:Leukocytes / Q000276:immunology; D054397:Receptors, CCR3; D019707:Receptors, Chemokine / Q000276:immunology; D011994:Recombinant Proteins / Q000276:immunology
D000911:Antibodies, Monoclonal; C111792:CCL18 protein, human; C515350:CCR3 protein, human; D019742:Chemokines, CC; D054397:Receptors, CCR3; D019707:Receptors, Chemokine; D011994:Recombinant Proteins; D016753:Interleukin-10