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)

Polymorphonuclear leukocytes have been implicated in connective tissue injury in a variety of disease processes. To gain insight into mechanisms by which neutrophils might degrade connective tissue macromolecules in the presence of proteinase inhibitors, we have used a model system that allows neutrophils to be held in vitro under physiologic conditions in close proximity to a very proteinase-sensitive substrate, (125)I-labeled fibronectin. We have found: (a) neutrophils spread rapidly on the fibronectin substrate; (b) fibronectin proteolysis by neutrophils is largely attributable to released elastase, and is linearly related to cell number over the range of 2,000 to 30,000 cells per assay; (c) oxidants released from neutrophils stimulated by opsonized zymosan or phorbol myristate acetate do not protect released elastase from inhibition by alpha(1)-proteinase inhibitor or alpha(2)-macroglobulin; (d) neutrophil myeloperoxidase and enzymatically generated superoxide anion render alpha(1)-proteinase inhibitor ineffective against fibronectin proteolysis when neutrophils are added 30 min later; and (e) alpha(1)-proteinase inhibitor and alpha(2)-macroglobulin incompletely inhibit fibronectin proteolysis by neutrophils (79.8+/-6.3 and 73.5+/-12.0%, respectively.) The data suggested that proteolysis due to neutrophils that are in contact with susceptible macromolecules may occur due to partial exclusion of inhibitors from the cell-substrate interface. Although confirming that alpha(1)-proteinase inhibitor is ineffective against neutrophil-derived proteolysis after exposure to oxidants, these studies did not support the hypothesis that oxidants released from stimulated neutrophils enhance activity of proteinases they release in the presence of alpha(1)-proteinase inhibitor. We anticipate that further studies with this test system will be helpful in defining conditions that modulate inflammatory connective tissue injury in diseases such as pulmonary emphysema and rheumatoid arthritis.
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PMID:Proteolysis by neutrophils. Relative importance of cell-substrate contact and oxidative inactivation of proteinase inhibitors in vitro. 618 Oct 97

In 20 patients with rheumatoid arthritis the plasma fibronectin concentrations were measured and correlated with the levels of C-reactive protein, alpha 1-antitrypsin, alpha 2-macroglobulin, fibrinogen, C3, C4 complement fractions and alpha 2-antiplasmin in serum respectively plasma. Patients with rheumatoid arthritis showed plasma fibronectin concentrations within reference levels. However, the concentrations of C-reactive protein, alpha 1-antitrypsin, alpha 2-antiplasmin, fibrinogen and C3-complement fraction were significantly higher in comparison to the healthy controls. The results indicate that fibronectin does not belong to the group of "acute phase proteins". Measurement of plasma fibronectin give no additional information about the activity of rheumatoid arthritis.
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PMID:[Fibronectin and other immunologic parameters in chronic polyarthritis]. 620 Oct 23

The presence of fibronectin on the surface of articular cartilage in rheumatoid arthritis (RA) was investigated. Cartilage samples were stained by the immunoperoxidase method using anti-human fibronectin antibody, and observed under light and electron microscopy. Fibronectin was present on the articular surface in 7 of 8 RA patients. The degree of staining varied greatly among the patients. Five of 8 patients were positive for fibronectin in 50% or more of the cartilage areas studied. In total, fibronectin was observed in RA. Fibronectin was not observed in cartilage samples of osteoarthritic joints or joints which were not diseased but had undergone trauma. Ultrastructurally, it was observed to be associated with collagen fibrils and amorphous substance in the matrix. The fibronectin-negative surface of the rheumatoid cartilage was usually thick ultrastructurally, compared with the fibronectin-positive surface, and the staining for fibronectin roughly correlated with decreased proteoglycans on the surface. The presence of fibronectin in the matrix appeared to be revealed by partial degradation of proteoglycans with proteolytic enzymes in the synovial fluid, as well as by the deposition of fibronectin onto the surface of rheumatoid cartilage. Fibronectin on the articular surface may play an important role in promoting pannus extension onto the articular surface in RA.
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PMID:Fibronectin on the surface of articular cartilage in rheumatoid arthritis. 620 43

Blood mononuclear cells from patients with rheumatoid arthritis produce the lymphokine, leukocyte inhibitory factor (LIF) in response to collagens in vitro, and blood monocytes release prostaglandins (PGE2) and a factor, mononuclear cell factor (MCF) which stimulates collagenase and PGE2 production by cultured synovial cells. We therefore examined the effect of collagens on the production of PGE2 and MCF. Blood mononuclear cells from 6 patients with rheumatoid arthritis and 6 normal subjects were cultured in native human types I, II, or III collagen-coated tubes, or with streptokinase-streptodornase (SK-SD), and the supernatant media derived from these cultures analyzed for the presence of MCF, PGE2, and LIF. Types II and III collagens, as well as SK-SD, markedly stimulated MCF production by the cells from all 12 subjects (MCF activity, expressed as a mean stimulation index (SI) +/- SEM, was 43 +/- 12 for type II, 33 +/- 7 for type III, and 37 +/- 23 for SK-SD). Type I collagen was less stimulatory (mean SI 10 +/- 7). Cells from the patients with rheumatoid arthritis, but not the normal subjects, produced LIF in response to types II or III collagens but not to type I collagen. PGE2 production by blood mononuclear cells paralleled that of MCF, although abrogation of PGE2 release with indomethacin did not reduce MCF production. alpha chains purified from denatured collagens also stimulated MCF production. Using cells from patients with rheumatoid arthritis, type II collagen stimulated production of all three factors in the presence of polymyxin B or fibronectin-depleted serum, suggesting, respectively, that neither endotoxin nor fibronectin were responsible for their generation. Monocytes, purified from normal blood by an adherence technique, but not lymphocytes depleted of monocytes, released MCF and PGE2 when cultured with type II collagen. These results demonstrate that collagens can act as ligands to stimulate monocytes, as well as antigens to stimulate sensitized lymphocytes, to produce soluble factors that may contribute to the destruction of connective tissue.
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PMID:Collagens act as ligands to stimulate human monocytes to produce mononuclear cell factor (MCF) and prostaglandins (PGE2). 630 48

The influence of plasma fibronectin on the cleavage of interstitial collagen types I, II, and III by mammalian collagenase was investigated. To this end, rheumatoid arthritis synovial tissue collagenase was isolated from tissue culture supernatants. A highly active enzyme preparation was obtained. Different dilutions of the collagenase were incubated in tubes coated with [3H]-labeled collagens. Liberation of labeled fragments in the presence (200 micrograms per ml) or absence of fibronectin was measured at different time intervals (1-30 min). A significant inhibition of collagen degradation was observed in case of type I and type III collagens. Analogous experiments were carried out using collagen-coated tubes preincubated with fibronectin at a concentration of 200 micrograms/ml. Here, a strong inhibition (76 percent) of type III collagen digestion by collagenase was observed, while the cleavage of type I or type II collagen was completely unchanged after preincubation with fibronectin. A direct attack of the collagenase preparation on plasma fibronectin could be excluded in control digestion experiments using radioiodinated fibronectin as substrate.
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PMID:Influence of plasma fibronectin on collagen cleavage by collagenase. 630 85

Normal synovial membranes and synovial membranes from patients with classic rheumatoid arthritis were investigated for the presence of fibrin and fibronectin by an indirect immunoperoxidase technique. In normal synovial membranes, fibronectin was found around the monolayer of the synovial lining cells. Staining was most intense on the surface and beneath the lining cells, but not detectable in the cytoplasm. Fibronectin was also found in the cytoplasm of the endothelial cells. No staining for fibrin was found in the normal synovial membrane. In synovial membranes from patients with rheumatoid arthritis, large amounts of fibronectin were found around the multilayer of synovial lining cells, in the cytoplasm of the endothelial cells, and in argyrophilic fiber-rich connective tissue. In superficial areas denuded of synovial lining cells, high amounts of fibronectin were found incorporated in fibrin. In some areas with noninjured synovial lining cells, fibrin was also found, but in this case no fibronectin was incorporated. No fibronectin was found in connective tissue in areas with infiltration of inflammatory cells. After treatment of normal and rheumatoid synovial membranes with hyaluronidase, fibronectin was still present around the lining cells but the staining was found to be more distinct. This study relates the presence of fibrin and fibronectin in the rheumatoid synovial membrane to the high amount of these proteins, recently described, in rheumatoid synovial fluid. It also suggests that fibronectin present in the synovial membrane is produced and secreted by the endothelial cells.
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PMID:Fibrin and fibronectin in rheumatoid synovial membrane and rheumatoid synovial fluid. 634 Jun 98

The distribution of fibronectin in the lining layer of inflamed rheumatoid arthritis (RA) synovium has been ultrastructurally investigated using an anti-human plasma fibronectin antibody. The hyperplasia of lining cells was prominent in the lining layer of the inflamed RA synovium. A high level of fibronectin was localized in this region. Ultrastructurally the fibronectin was observed on the surface of both type A (type M) and type B (type F) cells, and in the extracellular fibrin-like material. This glycoprotein was detectable in rough endoplasmic reticulum (RER), some Golgi apparatus, and peripheral vesicles of type B cells. On the other hand, RER and Golgi apparatus of type A cells failed to be immunostained with the antibody. Type A cells occasionally contacted each other with interdigitation of cytoplasmic processes, and a high amount of fibronectin was localized in this region. These findings indicate that fibronectin is synthesized along the classic secretory pathway through RER and Golgi apparatus of type B cells. On the contrary, type A cells seem not to be associated with the local synthesis of the glycoprotein. Fibronectin may play a structural role in organizing these proliferated lining cells by promoting cell adhesion. The synthesis of fibronectin by proliferated type B cells may be responsible in part for the local increase of this glycoprotein in the lining layer of RA synovium.
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PMID:The ultrastructural localization of fibronectin in the lining layer of rheumatoid arthritis synovium: the synthesis of fibronectin by type B lining cells. 635 36

The distribution of fibronectin in rheumatoid arthritis (RA) synovium has been investigated by light and electron microscopic immunohistochemistry using an antihuman fibronectin antibody. Heavy accumulation of fibronectin was observed in the lining layer and the areas of proliferation of fibroblasts. Rough endoplasmic reticulum (RER) and peripheral vesicles of proliferated type B lining cells and fibroblasts contained large amounts of fibronectin. Thus these cells seem to participate actively in the local synthesis and secretion of this glycoprotein. Type A lining cells and migrated mononuclear phagocytes contained many phagolysosomes in some of which dense accumulation of fibronectin was observed. Some of the materials in the phagolysosomes, with dense accumulation of fibronectin, resembled the fibrinous material-fibronectin complexes frequently seen in the pericellular spaces. Accordingly fibronectin seems to play a role in the clearance of fibrinous materials by these phagocytes. The proliferated capillaries and small vessels possessed multilamellated basement membranes with heavy accumulation of fibronectin. However, RER or Golgi apparatus of the endothelial cells contained no detectable amounts of fibronectin. This indicates that these cells do not actively participate in the synthesis of fibronectin and that the majority of this glycoprotein in the basement membranes originates in fibronectin from blood vessel exudate. Fibrinous material-fibronectin complexes were frequently seen on the endothelial cell surfaces. Circulating platelets and mononuclear cells occasionally came in contact with these complexes, suggesting an association of fibronectin with the formation and clearance of thrombi in the vascular lumina at the inflammatory sites of RA synovium.
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PMID:The localization of fibronectin in rheumatoid arthritis synovium by light and electron microscopic immunohistochemistry. 636 89

Argyrophilic reticulin fibres are an important component of the rheumatoid synovium and their distribution and that of their individual protein constituents have been studied in synovial biopsies from a series of 29 cases of rheumatoid arthritis. In acutely inflamed synovia they are predominantly found underneath the hyperplastic synovial lining layer and related to the inflammatory cell infiltrate. With developing chronicity the reticulin network is gradually replaced by mature collagen. This histological pattern is mirrored by changes in the individual components of reticulin fibres-fibronectin, the non-collagenous reticulin component of Pras and Glynn (NCRC) and collagen type III.
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PMID:Reticulin and its related structural connective tissue proteins in the rheumatoid synovium. 637 25

The localisation of fibronectin in the synovial membrane of rheumatoid arthritis (RA) and other chronic inflammatory joint diseases has been studied using a peroxidase-antiperoxidase immunohistochemical method. Synovia were studied from seven cases of seropositive RA three cases of seronegative RA, six cases of ankylosing spondylitis, four cases of Reiter's syndrome and five of psoriatic arthritis. Six were small biopsies and the remaining tissues were obtained at open surgery for orthopaedic procedures or biopsies. Fibronectin was demonstrated in all of the synovia examined and was present in intimal cells, synovial giant cells, the walls of small blood vessels, basement membrane of larger vessels and deposits of fibrin. No difference in this distribution of fibronectin was found in seropositive and seronegative RA, ankylosing spondylitis, Reiter's syndrome or psoriatic arthritis, neither was there any difference in the amount of fibronectin at various sites.
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PMID:Fibronectin in the synovium of chronic inflammatory joint disease. 637 32


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