Chen, Victoria Tsui Lin; (1996) Characterization of the interaction between monocytes and synovial fibroblasts in rheumatoid arthritis. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

A continuous presence of monocytes/macrophages in association with intimal synovial fibroblasts is observed in rheumatoid arthritis. Mononuclear cells infiltration is conspicuous in the earliest examples of synovitis and this observation points to a possible role for the two cell types in the onset of chronic inflammation. The chronic inflammation is characterized through the high content of inflammatory mediators such as IL-1β, IL-6 or TNF-α and the release of metalloproteinases and toxic oxygen metabolites. These latter products are thought to be instrumental in the ongoing erosion of cartilage and bone. The intimal synovial fibroblasts, with their constitutive VCAM-1 expression, may have a role in retention and subsequent priming or activation of monocytes in the synovial membrane. We developed a cell co-culture system, comprising of isolated synovial fibroblasts, monocytic U937 cells, hyaluronan (a component abundantly present in the synovial joint space) and human plasma rather than fetal bovine serum. Under these conditions, U937 cells adhere tightly to synovial fibroblasts (mediated by β1 and β2 integrins) and differentiate towards mature monocytes. We next analysed release of inflammatory mediators and toxic oxygen metabolites. The co-culture expresses high amounts of IL-6 but no detectable amounts of IL-1β or TNF-α. As a positive control we used phorbol ester treated U937 cells, which do release significant amounts of these mediators. Co-cultured cells did not release toxic oxygen metabolites, but did induce the synthesis of metalloproteinases in the synovial fibroblasts. In order to evaluate if the synovial fibroblasts distinguished themselves from other fibroblasts, with regards to the above mentioned parameters, we performed similar experiments with primary cultures of dermal fibroblasts. There was a quantitative difference, less monocytic cells bound to the dermal fibroblasts and a lower level of maturation was obtained, hut there was no qualitative difference between the two co-cultures.

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