Abstract
In patients with rheumatoid arthritis (RA), chemokine and chemokine receptor interactions play a central role in the recruitment of leukocytes into inflamed joints. This study was undertaken to characterize the expression of chemokine receptors in the synovial tissue of RA and non-RA patients. RA synovia (n = 8) were obtained from knee joint replacement operations and control non-RA synovia (n = 9) were obtained from arthroscopic knee biopsies sampled from patients with recent meniscal or articular cartilage damage or degeneration. The mRNA expression of chemokine receptors and their ligands was determined using gene microarrays and PCR. The protein expression of these genes was demonstrated by single-label and double-label immunohistochemistry. Microarray analysis showed the mRNA for CXCR5 to be more abundant in RA than non-RA synovial tissue, and of the chemokine receptors studied CXCR5 showed the greatest upregulation. PCR experiments confirmed the differential expression of CXCR5. By immunohistochemistry we were able to detect CXCR5 in all RA and non-RA samples. In the RA samples the presence of CXCR5 was observed on B cells and T cells in the infiltrates but also on macrophages and endothelial cells. In the non-RA samples the presence of CXCR5 was limited to macrophages and endothelial cells. CXCR5 expression in synovial fluid macrophages and peripheral blood monocytes from RA patients was confirmed by PCR. The present study shows that CXCR5 is upregulated in RA synovial tissue and is expressed in a variety of cell types. This receptor may be involved in the recruitment and positioning of B cells, T cells and monocytes/macrophages in the RA synovium. More importantly, the increased level of CXCR5, a homeostatic chemokine receptor, in the RA synovium suggests that non-inflammatory receptor–ligand pairs might play an important role in the pathogenesis of RA.
Highlights
Rheumatoid arthritis (RA) is a chronic inflammatory condition that affects multiple joints, and it results in the accumulation of leukocytes within the synovial tissue (ST) and synovial fluid (SF)
We examined chemokine receptor expression in ST taken from rheumatoid arthritis (RA) and non-RA patients using microarray technology, RT-PCR and immunohistochemistry
Patients and tissue selection Synovia were obtained from knee joints as this allowed the use of arthroscopic samples of non-RA as controls instead of osteoarthritic tissue, which can show more enhanced inflammatory changes
Summary
Rheumatoid arthritis (RA) is a chronic inflammatory condition that affects multiple joints, and it results in the accumulation of leukocytes within the synovial tissue (ST) and synovial fluid (SF). The pathogenesis of the RA is still largely unknown but leukocytes and their products play an important role in the development of inflammation, joint destruction and pain [2,3]. The attraction of leukocytes into the joints is controlled by chemokines, a family of small chemotactic cytokine-like molecules that act as potent mediators of inflammation [4]. Chemokine activity is dependent on the presence of and interaction with chemokine receptors on the leukocyte surface. Chemokines and their receptors are involved together in the development and perpetuation of inflammation [5]. In vitro and in vivo experiments have indicated that blocking chemokines or their receptors could potentially
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call