Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.4.24.3 (collagenase)
18,340 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Lymphocytes infiltrating synovial membranes were characterized in eight patients with proliferative rheumatoid synovitis. Surface immunoglobulins were studied with use of immunofluorescence, and the C3 receptor was detected by adherence of red cells coated with antibody and complement - both are B-cell markers. Spontaneous rosette formation with sheep erythrocytes was used as a T-cell marker. To obtain viable lymphocytes in suspension, the villous synovium of five of these patients was digested with collagenase and deoxyribonuclease. Populations enriched in lymphocytes could be obtained by velocity sedimentation. Whereas only 9 to 35 per cent of lymphocytes bore surface immunoglobulins, the majority (70 to 85 per cent) formed sheep-erythrocyte rosettes. Cells bearing the C3 receptor constituted a distinct minority of synovial lymphocytes in frozen-tissue sections, and were found in follicle-like accumulations. These data indicate that the predominant infiltrating lymphocyte in proliferative rheumatoid synovitis is a T cell.
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PMID:Predominantly T-cell infiltrate in rheumatoid synovial membranes. 16 88

Rabbits were injected intraarticularly three times with 0.5 ml of 10, 50 or 100 mg% purified rheumatoid synovial collagenase or with identical amounts of trypsin. 18 hours after the last injection the collagenase-injected animals showed distinct cellular exudation into the synovial fluid and acute arthritis; one week later there was a decrease of the cell count in the synovial fluid and appearance of proliferative synovitis, while 3 weeks later there was no exudation and less chronic inflammation but distinct fibrosis of the synovium. A direct action of collagenase on the connective tissue components would seem to be responsible for these changes. No pathologic alteration of the cartilage was observed. Trypsin-injected control animals showed negligible cellular exudation and no pathologic alteration of the synovium.
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PMID:Collagenase-induced experimental arthritis. 21 3

The Freund's adjuvant-injected rat shares a number of features with the arthritis patient, viz the presence of a proliferative synovitis, joint swelling, and cartilage and bone erosion. Naproxen, a prostaglandin synthetase inhibitor which is an effective antiinflammatory agent in laboratory animals and humans, was evaluated as an inhibitor of connective tissue destruction in this model by use of radiologic and histopathologic analyses. Sixteen days after rats were injected with Freund's complete adjuvant, marked joint swelling was noted. On day 17, vehicle or naproxen, 7 mg/kg/day, was administered orally. Twenty-eight days later vehicle-treated animals demonstrated the following pathologic changes in their hindpaws; swelling, cartilage loss, large amounts of pannus within the joint spaces, osteoporosis, bone erosions, periosteal new bone formation, heterotopic ossification, and bony ankylosis. Rats treated 28 days with naproxen had significantly milder disease than the vehicle controls. The incidence of severe juxtaarticular bone destruction was 10/10 in the vehicle controls versus 2/10 of the drug-treated group (P less than 0.01). A comparable reduction in cartilage erosion, incidence of pannus, and new bone formation was noted in the drug-treated group. These effects may relate to an inhibition of prostaglandin biosynthesis; prostaglandins have been shown to: 1) stimulate collagenase secretion from macrophages, 2) stimulate bone resorption in vivo and in vitro, and 3) diminish proteoglycan synthesis in cartilage.
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PMID:Effects of naproxen on connective tissue changes in the adjuvant arthritic rat. 51 18

The synovium removed from the knee of a 10-year-old with hemophilia A was characterized morphologically and biochemically. The specimen showed villous hypertrophy with hyperplasia of synovial lining cells which contained abundant intracytoplasmic granules of hemosiderin. Monolayer cultures prepared from enzymatically dispersed tissue were characterized by pigment-laden fibroblast-like cells and round cells. Both explants of synovium and adherent cells secreted a large amount of latent collagenase and neutral proteinase into the culture medium. The secretion of these enzymes dropped sharply and intracellular pigment decreased with passage of these cultures. Lysozyme was secreted by the explants but was not detected in the monolayer culture medium. These data establish the degradative potential of the synovitis found in hemophilia and support the concept that recurrent hemarthrosis without inflammation is sufficient in and of itself to produce proliferative synovitis.
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PMID:Proliferative synovitis in hemophilia: biochemical and morphologic observations. 62 83

There are two types of collagenases, products of two distinct genes, called MMP-1 (matrix metalloproteinase 1 or "fibroblast-type collagenase") and MMP-8 ("neutrophil collagenase"). In synovial fluid, MMP-8 is stored as latent proenzyme in polymorphonuclear neutrophils. MMP-8 is activated by hypochlorous acid produced by myeloperoxidase from hydrogen peroxide and chloride ion and by the hydroxyl radical produced in Haber Weiss reaction fed by superoxide produced by, eg, NADPH (reduced nicotinamide adenine dinucleotide) oxidase and xanthine oxidase. In addition to activation upon secretion, oxidatively modified MMP-8 is susceptible to a subsequent proteolytic attack and activation by cathepsin G. The authors suggest that activation of neutrophil-derived MMP-8 involves oxidative, nonproteolytic activation upon secretion and a more slowly progressive proteolytic activation by cathepsin G (or chymases and tryptases), and that these oxidative and proteolytic activation mechanisms act in concert. In contrast to MMP-8, MMP-1 is synthesized de novo and secreted immediately after synthesis by fibroblasts, macrophages, and some epithelial cells. Human rheumatoid synovial tissue contains mainly fibroblast-type MMP-1 collagenase as assessed by collagenase extracted from synovial tissue and by MMP-1 and MMP-8 immunostaining. It is suggested that in vivo, MMP-1 in synovitis tissue is activated by a plasminogen activator/plasminogen/prostromelysin (alternatively tryptases)/proMMP-1 cascade. In conclusion, MMP-8 and MMP-1 show type-specific compartmentalization and modes of activation in rheumatoid synovial fluid and tissue.
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PMID:Collagenase in synovitis of rheumatoid arthritis. 141 81

A number of cells, chemotactic factors, and inflammatory mediators are implicated in the complex mechanisms underlying crystal-mediated inflammation. Interleukin-8, released from mononuclear cells that have been exposed to urate and other crystals, is a potent chemotaxin and activator of neutrophils. Experimental and clinical observations suggest that joint movements, local biomechanical factors, and previous joint damage may play a role in influencing the intensity of microcrystalline synovitis and the distribution of articular and periarticular crystal deposits in both calcium pyrophosphate dihydrate crystal deposition disease and gout. There are rare reports of extra-articular calcium pyrophosphate dihydrate crystal deposition in tendons, bursae, dura mater, and ligamentum flavum (with radiculomyelopathy) and of massive "tumoral," tophuslike, periarticular calcium pyrophosphate dihydrate crystal deposits. Synovial fluid levels of ATP, the main substrate for nucleoside triphosphate pyrophosphohydrolase ectoenzyme, which cleaves ATP-releasing inorganic pyrophosphate, are higher in patients with calcium pyrophosphate dihydrate crystal deposition disease than in those with other arthritides, and the levels correlate with inorganic pyrophosphate concentrations. Further reports of acute calcific periarthritis of the first metatarsophalangeal joint (hydroxyapatite pseudopodagra) in young women have been described. The mitogenic response of fibroblasts to stimulation with basic calcium phosphate crystals is accompanied by induction and secretion of collagenase and neutral proteases, implicating a role for the crystals in the pathogenesis of both synovial proliferation and joint damage in chronic basic calcium phosphate crystal-associated arthropathy. Subcutaneous cholesterol crystal deposition with tophus formation is extremely rare and has been described in a patient with scleroderma and calcinosis cutis.
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PMID:Calcium pyrophosphate crystal deposition disease and other crystal deposition diseases. 150 84

Substrate specificity studies of collagenase extracted from human rheumatoid synovium suggest that synovial pannus tissue overlying articular cartilage may not be particularly active in degradation of cartilage type II collagen, which, considering the poor inherent healing capacity of the articular hyaline cartilage, may exert a protective function against inadvertant tissue damage. Rheumatoid synovial tissue was also used to establish synovial fibroblast cell lines. Treatment of these cells in monolayer cultures with IL-1 leads to collagenase gene activation, increased collagenase production and an almost complete autoactivation of secreted collagenase. Interleukin-1 also activated stromelysin gene suggesting this as a possible mechanism effecting autoactivation. Latent human fibroblast and macrophage collagenase purified from culture medium were efficiently activated by phenylmercuric chloride but also by gold thioglucose, gold sodium thiomalate and HCIO. These new observations support the Cys73 switch activation mechanism. In contrast to neutrophil collagenase, the activation by gold(I) compounds and HCIO was associated with a change in the apparent molecular weight of the fibroblast procollagenase. In addition, gold(I) compounds rendered collagenase more susceptible to thermal denaturation. Thus the fibroblast-type interstitial collagenase, probably derived from fibroblast- and macrophage-like synoviocytes, seems to provide the predominant collagenolytic potential in human rheumatoid synovial tissue. Furthermore, the conditions in synovitis tissue may be such as to favor at least initial activation of collagenase synthesized and secreted in situ.
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PMID:Substrate specificity and activation mechanisms of collagenase from human rheumatoid synovium. 166 9

Arthritis was induced by injecting cationic amidated bovine serum albumin (aBSA) (pI approximately 9.2) into the knee joint of immunized guinea pigs and the mechanisms of articular cartilage destruction were studied morphologically and biochemically. Marked synovitis associated with polymorphonuclear leukocyte (PML) infiltration occurred within 1 day of the challenge. Articular cartilage infiltrated by PMLs was almost completely destroyed after 2 weeks. During the initial destructive process, proteoglycans were depleted from the cartilage and later collagen fibers disappeared. Granulation tissue growing in the inflamed synovium and bone marrow replaced the destroyed cartilage and joint cavity and formed fibrous scar tissue (fibrous ankylosis) by 8 weeks. Subsequently, the knee joints developed cartilagenous ankylosis by 12 weeks and finally bony ankylosis at 28 weeks. Autoradiography using 125I-aBSA and immunofluorescence studies for immunoglobulin (IgG) and complement (C3) demonstrated that the antigen is trapped in all zones of the articular cartilage and serves as a trigger for immune complex formation. Significantly increased neutral proteinase activities against substrates of proteoglycan subunits, [3H]carboxymethylated transferrin and L-pyroglutamyl-L-prolyl-L-valine-paranitroanilide were detected in homogenates of the synovium and cartilage from arthritic knee joints 1 and 2 weeks after induction. Inhibitor studies and pH curves suggested that the proteinase is leukocyte elastase. Measurable amounts of gelatinolytic activity, detected by activation with 4-aminophenylmercuric acetate and inhibited with EDTA, were also present in the same samples, but there was no detectable collagenase activity. The data on SDS-gelatin substrate gel showed that the proteinase is gelatinase derived from PMLs. These results suggest that in aBSA-induced arthritis, elastase and gelatinase from PMLs invading articular cartilage may play important roles in cartilage destruction.
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PMID:Arthritis induced immunologically with cationic amidated bovine serum albumin in the guinea pig. A morphological and biochemical study on the destruction of articular cartilage. 167 78

Amiprilose HC1 (SM-1213), a nontoxic modified hexose sugar, was evaluated in in vivo and in vitro models of synovitis. In 8 sequential trials, 90 Louvain (LOU) rats and 91 Sprague-Dawley (SD) rats were immunized with chick type II collagen and given amiprilose HC1 in water (1 mg/ml) or water alone. In the LOU rats, the arthritis incidence was 7/46 (15%) in the amiprilose HC1 group vs 16/44 (36%) in the water group (p less than 0.01). In the SD rats, the incidence was 28/46 (60%) in the experimental vs 33/45 (73%) in the control group (p greater than NS), although the prevalence of arthritis on Days 16 and 21 was significantly (p less than 0.03) lower in the experimental group. Amiprilose HC1 did not affect the antibody titers or delayed-type hypersensitivity to collagen, or T cell subset distribution in the LOU experiments. Two analogues, SM-1211 and SM-1212, did not alter this disease. No toxicity was noted. At a nontoxic concentration of 1 mg/ml, amiprilose HC1 suppressed 3H thymidine incorporation in cultured rabbit synovial fibroblasts by 78% and resulted in the appearance of numerous intracytoplasmic granules/vacuoles. These effects were partially antagonized by indomethacin or dexamethasone at 10(-7) M. SM-1211 was inert in this system. Amiprilose HC1 system also reduced rabbit synoviocyte supernatant prostaglandin E2 levels up to 73% in a dose related fashion, but did not affect collagenase activity. These morphologic changes in synoviocytes, combined with anti-inflammatory and antiproliferative effects, provide evidence that amiprilose HC1 possesses modest and nontoxic antirheumatic properties. A search for analogues of this sugar with more substantial clinical activities is warranted.
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PMID:Evaluation of a modified hexose sugar, amiprilose hydrochloride, in experimental models of synovitis. 278

Native serum C1q, the collagenous-like subcomponent of the first component of complement, is not recognized by polyclonal anti-collagen type II antibodies. However, when purified C1q was subjected to limited proteolysis by collagenase it showed antigenic cross-reactivity with collagen type II. The same cross-reactivity was observed with hemolytically active C1q in synovial fluids of patients with rheumatoid arthritis (RA), whereas C1q from synovial fluids of patients with osteoarthritis (OA), villo-nodular synovitis and ankylosing spondylitis was not recognized by this antibody. However, incubation of synovial fluid C1q of OA patients with synovial fluid leucocytes from RA patients led to an alteration of OA-C1q which was now recognized by the anti-collagen type II antibody.
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PMID:Enzymatic alteration of C1q, the collagen-like subcomponent of the first component of complement, leads to cross-reactivity with type II collagen. 283 Jan 44


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