The chemoattraction of lymphocytes by rheumatoid arthritis - synovial fluid is not dependent on the chemokine receptor CCR5.
OBJECTIVE
The objective was to study the potential role of the chemokine receptor CCR5 in the chemoattraction of lymphocytes by rheumatoid arthritis synovial fluid (RA-SF).


METHODS
The expression of the CCR5 receptor was studied by flow cytometry. Chemotaxis of peripheral blood lymphocytes in response to RA-SF was analyzed on transmigration chambers. Chemotaxis of immortalized lymphocytes from individuals homozygous for the Delta32 deletion of the CCR5 gene (CCR5-/-) was analyzed. The effect of a neutralizing anti-CCR5 antibody on the migration of CCR5+/+ cells was also studied.


RESULTS
We confirmed an increase in the proportion of CCR5-expressing lymphocytes in RA-SF and a preferential migration of CCR5+ lymphocytes toward RA-SF in vitro. CCR5-/- lymphocytes showed decreased chemotactic responses to the chemokine MIP-1beta but not to RA-SF. The chemotactic responses of CCR5+/+ lymphocytes to RA-SF were not modified by anti-CCR5 neutralizing antibody.


CONCLUSIONS
We confirm a preferential accumulation of CCR5-expressing lymphocytes into RA-SF. However, the chemotactic responses of lymphocytes to RA-SF were not dependent on a functional CCR5 receptor, suggesting that CCR5 is a marker of a lymphocyte subset rather than a specific mediator of chemotactic responses to chemokines in RA-SF.
Unidad de Investigación and Servicio de Reumatología, Hospital 12 de Octubre, 28041 Madrid, Spain.
B
B
Santiago
M
M
Galindo
M
M
Rivero
M T
MT
Brehmer
I
I
Mateo
J L
JL
Pablos
D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D001172:Arthritis, Rheumatoid; D002465:Cell Movement / Q000187:drug effects / Q000276:immunology; D002472:Cell Transformation, Viral; D002478:Cells, Cultured; D002630:Chemotactic Factors / Q000096:biosynthesis* / Q000494:pharmacology; D002633:Chemotaxis; D005434:Flow Cytometry; D006720:Homozygote; D006801:Humans; D009500:Neutralization Tests; D019713:Receptors, CCR5 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D013582:Synovial Fluid / Q000378:metabolism*; D013601:T-Lymphocytes / Q000187:drug effects / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D002630:Chemotactic Factors; D019713:Receptors, CCR5