Abstract
Synovial fluid from patients with various arthritides contains procoagulant, cell-derived microparticles. Here we studied whether synovial microparticles modulate the release of chemokines and cytokines by fibroblast-like synoviocytes (FLS). Microparticles, isolated from the synovial fluid of rheumatoid arthritis (RA) and arthritis control (AC) patients (n = 8 and n = 3, respectively), were identified and quantified by flow cytometry. Simultaneously, arthroscopically guided synovial biopsies were taken from the same knee joint as the synovial fluid. FLS were isolated, cultured, and incubated for 24 hours in the absence or presence of autologous microparticles. Subsequently, cell-free culture supernatants were collected and concentrations of monocyte chemoattractant protein-1 (MCP-1), IL-6, IL-8, granulocyte/macrophage colony-stimulating factor (GM-CSF), vascular endothelial growth factor (VEGF) and intracellular adhesion molecule-1 (ICAM-1) were determined. Results were consistent with previous observations: synovial fluid from all RA as well as AC patients contained microparticles of monocytic and granulocytic origin. Incubation with autologous microparticles increased the levels of MCP-1, IL-8 and RANTES in 6 of 11 cultures of FLS, and IL-6, ICAM-1 and VEGF in 10 cultures. Total numbers of microparticles were correlated with the IL-8 (r = 0.91, P < 0.0001) and MCP-1 concentrations (r = 0.81, P < 0.0001), as did the numbers of granulocyte-derived microparticles (r = 0.89, P < 0.0001 and r = 0.93, P < 0.0001, respectively). In contrast, GM-CSF levels were decreased. These results demonstrate that microparticles might modulate the release of chemokines and cytokines by FLS and might therefore have a function in synovial inflammation and angiogenesis.
Highlights
Cell-derived microparticles, predominantly from platelets and erythrocytes, are present in human blood
We demonstrated recently that synovial fluid from the inflamed joints of rheumatoid arthritis (RA) and arthritis control (AC) patients contains cell-derived microparticles
Cellular origin of synovial microparticles Previously, we found no differences between the numbers and cellular origin of microparticles in synovial fluid from RA and AC patients [4]
Summary
Cell-derived microparticles, predominantly from platelets and erythrocytes, are present in human blood. The presence of such microparticles has been associated with the activation of coagulation [1,2,3]. We demonstrated recently that synovial fluid from the inflamed joints of rheumatoid arthritis (RA) and arthritis control (AC) patients contains cell-derived microparticles. These microparticles originate from monocytes and granulocytes, and to a smaller extent from lymphocytes [4]. Synovial microparticles are strongly procoagulant via an initiation mechanism dependent on tissue factor and factor VII(a). We proposed that such microparticles might contribute to the local formation of fibrin clots, the so-called rice bodies
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