Abstract
A massive accumulation of inflammatory cells in synovial tissues is a major pathological feature of rheumatoid arthritis (RA). Neutrophiles dominate synovial fluid while rheumatoid synovium is infiltrated with mononuclear cells. Mechanisms regulating influx of particular subpopulations of leukocytes into articular cavity and synovium compartment are not completely defined. An increasing amount of data supports a crucial role of a C-C chemokine RANTES in the RA pathogenesis. Our objective is to evaluate chemotactic activity for neutrophils (NCA), lymphocytes (LCA), and monocytes (MoCA) in SFs obtained from patients with RA and osteoarthritis (OA). We also aimed to characterise the relation between chemotactic activity, RANTES, and percentage distribution of leukocytes in SF. SFs from 11 patients with RA and 6 with OA were included in the study. Modified microchamber Boyden method was employed to assess chemotactic activity. Cytological and biochemical analysis of SF was performed. RANTES was measured with ELISA. Rheumatoid SFs were rich in cells with predominance of neutrophiles while osteoarthritic fluids were lymphocytic. RA SFs were also characterised by increased lactoferrin level. Both NCA and LCA were higher in SF from patients with RA (62 ± 12 and 24 ± 6 cells/HPF, resp) as compared to patients with OA (23 ± 6; P < .05 and 6 ± 2 cells/HPF; P < 0.05). The chemoattractive effect of RA SF was more pronounced on neutrophiles than on lymphocytes. RA SF expressed high RANTES levels (145 ± 36 pg/mL), while OA SF was characterised by only trace amount of this chemokine (2 ± 1 pg/mL). We found positive correlation of RANTES with chemotactic activity for mononuclear cells (LCA+MoCA; R = 0.61; P < .05). Surprisingly, RANTES correlated also positively with neutrophiles number (R = 0.77; P < 0.001). Rheumatoid SF possesses strong chemotactic potency for leukocytes. RANTES is overexpressed in RA SF and is a potential mediator influencing intensity and composition of cellular infiltration in joints affected with inflammatory arthritis.
Highlights
The synovial fluid (SF) in rheumatoid arthritis (RA) is characterised by increased cellularity with predominance of neutrophils
We have demonstrated that synovial fluids from RA patients express strong chemotactic activity towards peripheral blood leukocytes
Neutrophils were the strongest population attracted by the SF, which is in line with previous reports [7, 8]
Summary
The synovial fluid (SF) in rheumatoid arthritis (RA) is characterised by increased cellularity with predominance of neutrophils. Cells accumulating in rheumatoid tissues produce a number of mediators including cytokines and prostanoids, which play a crucial role in the progression of inflammation and tissue damage [1]. Migration of leukocytes into the extravascular space is the main stage in the development of cellular infiltration. This phenomenon depends on both the expression of adhesion molecules on the endothelial cells and the gradient of chemotactic factors produced at the site of inflammation. Among various chemotactic factors (weakly characterised) chemokines constitute a group of important mediators, and the major role of RANTES (regulated upon activation, normal T cell expressed and secreted), a C-C family derived chemokine, in RA has been established. The percentage of lymphocytes and monocytes with the CCR5 receptor expression (with RANTES as a main ligand) in the rheumatoid SF many times exceeds the value observed in the peripheral blood [4, 5]
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