Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0003873 (rheumatoid arthritis)
 53,068 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Immune-complex-mediated vasculitis is a frequent complication of rheumatoid arthritis and systemic lupus erythematosus. The mechanism of deposition of immune complexes within the vessel wall in these diseases remains unknown, but probably involves other proteins. Fibronectin is a likely candidate since it possesses the ability to bind to collagen, endothelial cells, and possibly immunoglobulins and immune complexes. In this study, the binding of fibronectin to IgG and IgM cryoglobulins, cold soluble IgM, IgG, IgG subclasses and IgG fragments was investigated in the solution phase. Static light scattering, fluorescence anisotropy, fluorescence intensity, and PEG precipitation studies were used to investigate binding under different conditions of temperature and ionic strength. These studies failed to demonstrate significant binding between fibronectin and IgM, IgG, IgG subclasses and IgG fragments under the conditions studied. These findings argue against solution phase binding of fibronectin and immunoglobulins contributing to immune complex vasculitis. The possibility of important surface interactions between these proteins has not been ruled out.
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PMID:Lack of binding between cryoimmunoglobulins, immunoglobulins and fibronectin: implications for immune complex vasculitis. 182 33

The VLA-4 (CD49d/CD29) integrin is a cell surface receptor involved in the interaction of lymphoid cells with both extracellular matrix (ECM) and endothelial cells. We have investigated the expression and function of VLA-4 fibronectin (FN) receptors on T cells localized in the inflammed synovium of patients with rheumatoid arthritis (RA). A high proportion of T cells in both synovial membrane (SM) and synovial fluid (SF) expressed the activation antigens AIM (CD69) and gp95/85 (Ea2) as well as an increased number of VLA-4 alpha and beta 1 adhesion molecules, as compared with peripheral blood (PB) T cells from the same patients. Furthermore, the majority of these activated SF T cells were able to adhere to a 38-kD FN proteolytic fragment containing the connecting segment-1 (CS-1) specifically through VLA-4 receptors, whereas a significantly lower proportion of PB T cells displayed this capacity. Therefore, our results show that activated T cells selectively localize at sites of tissue injury in RA disease and provide evidence for the in vivo regulation of the expression and function of the VLA-4 integrin. This regulatory mechanism may enable T cells either to facilitate migration or to persist at sites of inflammation.
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PMID:Upregulated expression and function of VLA-4 fibronectin receptors on human activated T cells in rheumatoid arthritis. 183 Aug 91

The presence of circulating IgG, IgA and IgM antibodies to native cartilage collagens in some patients with rheumatoid arthritis (RA) suggests that an autoimmune response to cartilage collagens may be involved in the pathogenesis of RA. However, the relevance of such antibodies to the pathological process remains unclear, and it is likely that many humoral and cellular derived factors combined to trigger events leading to the chronicity of the rheumatoid lesion. Since histological and biochemical studies have suggested the involvement of mast cells in the rheumatoid joint, we have studied the frequency of IgE antibodies directed against the cartilage collagens type II, IX and XI in patients with active rheumatoid disease. Of the 91 patients' sera tested, 32 had significant levels of IgE anti-cartilage collagen antibodies when compared with non-arthritic controls. Total serum IgE levels did not correlate with the presence of IgE anti-collagen antibodies, nor were any patients positive for IgE antibodies to fibronectin, a widely distributed extracellular matrix component. These results are consistent with an allergic type I hypersensitivity reaction to cartilage antigens in RA involving mast cell and basophil degranulation.
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PMID:Serum IgE anti-cartilage collagen antibodies in rheumatoid patients. 186 71

Metabolism of fibroblasts plays a key role in wound healing, fibrosis, rheumatoid arthritis, and similar physiological and pathological processes. The regulatory influence of eicosanoids, an important class of inflammatory mediators, on fibroblast metabolism, in these processes is, to date, unclear. The aim of this study was to investigate the effect of some eicosanoids on chemotaxis and protein synthesis of fibroblasts in vitro. Of twelve eicosanoids tested, only 5(S)-HETE, LTB4, and 12(S)-HETE were active as chemo-attractants for fibroblasts. 5(S)-HETE was the most potent attractant. It exerted its maximal activity at 10(-10) mol/l. 12(S)-HETE and LTB4 caused similar dose dependent fibroblast chemotaxis with a maximum of activity at 10(-7) M and 5 x 10(-8) M, respectively. Hydroxylation of LTB4 on C20 or methylation of the carboxy group of 12(S)-HETE decreased reactivity of the parent compounds only slightly. Eicosanoid induced chemotaxis could be antagonized by 12(S)-HETE but not by the proteinaceous chemoattractants fibronectin, PDGF, or EGF. Receptors for peptide and eicosanoid mediated chemotaxis are thus different. Inhibition of collagen synthesis was observed in the presence of 5(S)-HETE and 12(S)-HETE while total protein synthesis was unaffected by 12(S)-HETE and augmented by 5(S)-HETE. These data suggest that certain eicosanoids specifically regulate fibroblast activities in wound healing and similar events of connective tissue reorganization.
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PMID:Influence of eicosanoids on fibroblast chemotaxis and protein synthesis in vitro. 196 52

Autoimmune MRL-lpr mice develop a spontaneous arthritis displaying similar articular and extra-articular features to rheumatoid arthritis in humans. In this study we used an ELISA assay to evaluate the serological responses of MRL-lpr mice to select extracellular matrix proteins associated with the joint. Significant levels of antibodies to collagens types I, II, III, IV, and V were demonstrated starting between 17 and 20 weeks of age. Moreover, the sera contained a strong reactivity to fibronectin. Responses to proteoglycans and laminin were weaker but still detectable. Specificity studies on pooled sera from MRL-lpr mice suggest that the autoantibodies produced are highly cross-reactive. The results indicate that the MRL-lpr mouse strain exhibits similar anti-extracellular matrix antibody profiles to those seen in varying frequencies in the sera and synovial fluid of patients with rheumatoid arthritis.
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PMID:Antibodies to extracellular matrix proteins in the sera of MRL-lpr mice. 200 42

Fragments of bovine plasma fibronectin produced by cathepsin D digestion are reportedly mitogenic for hamster fibroblasts. Rheumatoid arthritis synovial fluid contains many fibronectin fragments, which may contribute to the proliferation of synovial cells. We have therefore investigated the potential of fibronectin fragments to stimulate proliferation of synovial fibroblast-like cells using human material. Affinity-purified human plasma and synovial fluid fibronectin was digested with cathepsin D at pH 3.5 for 0-18 h and proteolysis stopped with pepstatin. A variety of fragments were produced ranging from 50 to 200 kDa when analysed by SDS-PAGE. The proliferative activity of various test preparations was studied using quiescent human skin and synovial fibroblasts. Tests were applied for 24 h to 10(4) cells and DNA synthesis measured by tritiated thymidine incorporation. Both undigested and peptides of fibronectin consistently failed to stimulate DNA synthesis in fibroblasts at all concentrations tested, compared with a phosphate-buffered saline control. This was in marked contrast to human synovial fluid from either rheumatoid arthritis or osteoarthritis patients, which stimulated DNA synthesis in the same system (P less than 0.01). Therefore, our data do not confirm the findings of previous studies in which animal materials were used. We can find no evidence that fibronectin fragments play a role in stimulating synovial proliferation in inflammatory arthritis.
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PMID:Synovial fluid fibronectin fragments: no evidence for a mitogenic effect on fibroblasts. 207 72

Fibronectin is a known component of plasma cryoprecipitates. It is seen in cryoglobulins from patients with monoclonal gammopathies and also from rheumatoid arthritis, and patients with systemic lupus erythematosus and other connective tissue diseases. We evaluated the clinical relevance of measures of cryoprecipitable fibronectin from the sera of 88 patients with rheumatic diseases and 27 healthy controls. There were 28 patients with rheumatoid arthritis, 19 with systemic vasculitis, 5 with cutaneous vasculitis, and 36 with a systemic connective tissue disorder. We measured total and cryoprecipitable fibronectin and for comparison immunoglobulins G, A, and M and complement C3 and C4. Cryoprecipitable fibronectin was detected in 33% control sera and 42% patient sera. The mean levels were higher in the sera of patients in all diagnostic groups. The highest levels were seen in rheumatoid patients with systemic disease, systemic vasculitis, and connective tissue diseases. The presence of cryoprecipitable fibronectin was related to the clinical activity of systemic vasculitis; none of the 6 patients with clinically inactive vasculitis had detectable fibronectin in their cryoprecipitates; but it was seen in 7 to 13 cases with active vasculitis. There were only weak relationships between cryoprecipitable fibronectin and immunoglobulin and complement levels in cryoprecipitates. We conclude that routinely measuring fibronectin levels in cryoprecipitates is generally of doubtful diagnostic value. However, it appears to be a useful marker of the clinical activity of systemic vasculitis and we recommend its use in the laboratory assessment of vasculitis.
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PMID:Diagnostic relevance of fibronectin in cryoprecipitates. 234 38

In rat studies, fibronectin (Fn), a ubiquitous glycoprotein, is a T-cell mitogen and stimulates the production of interleukin 1 by peritoneal exudate macrophages. In contrast, Fn has no mitogenic activity for human lymphocytes and does not stimulate interleukin 1 release by human peripheral blood mononuclear cells. Fn increases in vitro peripheral blood mononuclear cell phytohemagglutinin responses in normals and patients with active, but not inactive, rheumatoid arthritis. Fn may alter local immunoregulation and play an active role in the rheumatoid synovial lesion.
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PMID:Modulatory effects of fibronectin on in vitro lymphocyte responses. 239 Aug 49

Synovial tissue from patients with rheumatoid arthritis was enzymatically dissociated, and single cell suspensions were fractionated into subpopulations by centrifugation on continuous Percoll gradients. Five fractions (F1-F5) with densities of 0.991-0.998 gm/ml, 0.998-1.042 gm/ml, 1.042-1.062 gm/ml, 1.062-1.082 gm/ml, and 1.082-1.180 gm/ml, respectively, were prepared. F3 consistently contained the highest number of macrophages, while F2 and F4 contained substantially fewer macrophages. Macrophages present in F2, F3, and F4 were enriched by differential adherence to fibronectin-coated collagen gels. These macrophage-enriched cell preparations were found to be Fc and C3 positive, esterase positive, and peroxidase negative, to stain positively with anti-HLA-DR, anti-Leu-M3, OKM1, and OKM5 monoclonal antibodies, and to show characteristic features of macrophages by electron microscopy. Macrophages from F3 consistently induced neovascularization in rat corneas, while equal numbers of macrophages from F2 and F4 did not. Fibroblastic synovial cells and cells that did not adhere to fibronectin-coated collagen gels did not induce neovascularization. Within the rheumatoid synovium, there appears to be a major subpopulation of macrophages capable of inducing neovascularization, a process vital to the development of the rheumatoid synovial pannus.
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PMID:Stimulation of neovascularization by human rheumatoid synovial tissue macrophages. 242 91

Biopsies from the temporal artery of 32 patients suspected of giant-cell arteritis were evaluated retrospectively by light microscopy, histochemical, and immunohistochemical methods, as well as by transmission electron microscopy (TEM). At the clinical follow-up the 32 patients included four clinical groups: temporal arteritis (8 patients), polymyalgia rheumatica (10 patients), rheumatoid arthritis (4 patients), and a group of miscellaneous diseases unrelated to inflammatory rheumatic diseases (10 patients). There were a number of similarities between age-related alterations in the arteries and the changes in giant-cell arteritis. The most important differences were the inflammatory cellular infiltration of the media, the perifocal accumulation of fibronectin, and the occurrence of deposits of fibrin/fibrinogen and fibrin/fibrinogen degradation products. In addition, alpha-2 macroglobulin, lysozyme and factor VIII were also noted in giant-cell arteritis. The alterations in giant-cell arteritis show a number of similarities to the changes following experimental vascular injury of the rabbit aorta. The nature of the findings in human giant-cell arteritis, as well as the similarity to the experimental arteritis, indicate that giant-cell arteritis may reflect a non-specific reaction to injury, independent of the cause of the disease.
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PMID:Giant-cell arteritis. Histological, immunohistochemical and electronmicroscopic studies. 244 62


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