Fibronectin promotes macrophage adherence and expression of Fc receptors, is chemotactic for fibroblasts, and is an opsonin for fibrin and denatured collagen. These properties suggest a role for fibronectin in the modulation of joint inflammation. Since structural modification of the fibronectin molecule has been shown to result in loss or de novo acquisition of opsonic and chemotactic activity, we determined the functional and immunochemical properties of fibronectin isolated from the inflamed joint. Eighty‐six percent of synovial fluids obtained from patients with active rheumatoid arthritis (RA) contained fibronectin fragments, and 39% of the fluids no longer displayed the dimeric form. Compared with native fibronectin, RA peptides were as active in promoting synoviocyte chemotaxis and in glycosaminoglycan binding, but displayed lower affinity for fibrin and gelatin. Although comparable with intact protein in augmenting monocyte attachment to gelatin, the RA synovial fluid peptides did not augment monocyte attachment to fibrin. Analysis of whole synovial fluid and isolated fibronectins by enzyme immunoassay showed that the increased fibronectin immunoreactivity, previously reported in RA synovial fluid, measures intact and nearly intact protein and does not measure extensively degraded fragments.

Large quantities of fibronectin (Fn) are present in inflammatory synovial fluid. Inflammatory synovial fluid Fn, while indistinguishable from plasma Fn on the basis of reactivity to polyclonal antibodies, displays alterations in molecular size and charge. Since biochemical differences between plasma and synovial fluid fibronectins might be in part due to differences in glycosylation we have compared the carbohydrate composition of plasma Fn, synovial fluid Fn, and Fn from synoviocyte conditioned medium by biochemical assay, glycopeptide analysis, and binding to a series of lectins.Synovial fluid Fn has a greater carbohydrate content but contains less sialic acid when compared with plasma Fn. Glycopeptides formed from synovial fluid Fn are smaller than plasma Fn glycopeptides. These data suggest the presence of an additional N-linked oligosaccharide chain on synovial fluid Fn. In addition, synovial fluid Fn contains N-acetyl galactosamine indicating the presence of 0-linked oligosaccharides. Synovial fluid Fn and Fn isolated from rheumatoid synoviocyte-conditioned medium display strong reactivity with the lectins wheat germ agglutinin (WGA) and peanut agglutinin (PNA), whereas normal and rheumatoid plasma Fn react weakly. The PNA reactivity of synovial fluid Fn is mediated by terminal ,-galactose residues on the gelatin-binding domain, whereas the enhanced WGA reactivity of synovial Fn is mediated by a sialic acid containing oligosaccharide located on a 27-kD C-terminal fragment. These data demonstrate domainspecific biochemical differences between plasma and synovial fluid fibronectins. These differences suggest a local origin for synovial fluid Fn and may contribute to functional differences between these forms of the protein.

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We examined fibronectin synthesis, secretion, and deposition in vitro by primary explants of rheumatoid synovium. Primary cultures initiated from tissue with monocytic infiltrates had higher levels of fibronectin synthesis; addition of dexamethasone at concentrations known to stimulate other tissue fibroblasts increased fibronectin synthesis and secretion. Newly synthesized fibronectin recovered from primary rheumatoid culture medium had a higher apparent molecular weight (240-245 kd), on sodium dodecyl sulfate-polyacrylamide gel electrophoresis, compared with fibronectin recovered from passaged normal and rheumatoid cultures (230 kd). Primary rheumatoid explant cultures had a characteristic morphology which correlated with fibronectin deposition. Dense deposits of fibronectin extracellular matrix covered overlapping synoviocytes adjacent to esterase-positive mono-