Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.11.1.7 (peroxidase)
 65,474 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In order to determine the possible mechanisms whereby interactions between phagocytic cells and crystals of monosodium urate (MSU) lead to cell death with simultaneous release of both cytoplasmic and lysosomal enzymes, phagocytic leukocytes of the smooth dogfish shart Mustelus canis were studied by means of light and electron microscopy, and biochemistry. Lysosomes of these cells can be stained supravitally with toluidine blue and are large enough (0.7-0.8 mu) to be clearly resolved with the light microscope. Light microscopic observations showed that of cells exposed to MSU 87% of those containing visible ingested crystals died within 1 hour, whereas 92% of adjacent cells in the same wet mount without such srystals survived. Cell death occured after a latent period of 10-15 minutes following fusion of lysosomes with crystal-containing phagosomes. Electron microscopic examination of both dogfish and human leukocytes exposed to MSU for more than 1 hour and then fixed in situ revealed occasional discontinuities or ruptures in secondary lysosome membranes. Endogenous peroxidase activity could be cytochemically localized in primary and secondary lysosomes and in the cytoplasm adjacent to such ruptured secondary lysosomes. It was not seen adjacent to primary lysosomes, a result indicating that the cytoplasmic reaction product was not a diffusion artifact. To exclude the possibility that crystals were exercising their affect primarily upon the plasma membrane, suspensions of dogfish buffy coat cells were incubated with cytochalasin B (5 mug/ml, 10 minutes), which inhibits phagocytosis but not exocytosis of lysosomal enzymes by stimulated phagocytes. Whereas cells exposed to MSU crystals released 30% of their content of lysosomal beta-glucuronidase activity and 28% of their cytoplasmic lactate dehydrogenase (LDH) activity within 3 hours, preincubation with cytochalasin B reduced the release of LDH activity within that period to 6% but reduced the release of beta-glucuronidase activity only to 20%. Preincubation with 10-3 M cyclic adenosine monophosphate (cAMP) and theophylline (10-3 M), which inhibit lysosomal fusion, reduced the release of both LDH and beta-glucuronidase activities to 7% and 6% respectively. Cells that were preincubated with both cytochalasin B and cAMP + theophylline released only 1% LDH activity and 4% beta-blucuronidase activity. These results are compatible with the "suicide sac" hypothesis of lysosomal enzyme release mediated by MSU for the following reasons: a) cell death was seen to follow uptake, not mere exposure to crystals, b) ultrastructural studies indicated that the primary injury was to the secondary lysosome membrane, and c) cell death was reduced when either phagocytosis or lysosomal fusion was inhibited.
Arthritis Rheum
PMID:Mechanisms of lysosomal enzyme release from leukocytes. IV. Interaction of monosodium urate crystals with dogfish and human leukocytes. 4 82

Horseradish peroxidase (HRPO) conjugated with goat antihuman IgG, goat antihuman IgM, and aggregated human IgG has been used as a enzymatic marker to stain IgG, IgM, and rheumatoid factor in rheumatoid cartilage. When Hrpo-anti IgG and HRPO-anti IgM were used, immunoglobulin deposits were not observed in nonrheumatoid cartilage. However 7 of 8 rheumatoid cartilage specimens stained with HRPO-anti IgG showed electron-dense deposits. Three rheumatoid specimens stained with HRPO-anti IgM showed similar findings. Both of 2 rheumatoid specimens also stained positively with HRPO conjugated with aggregated IgG, a finding indicating that rheumatoid factor was present. The deposits were seen between the collagen fibers of the superficial layer of the cartilage to a maximal depth of 22 mu from the surface (average: 7 mu). The amorphous fibrinous material on the surface of the cartilage was also stained. The demonstration of IgG, IgM, and rheumatoid factor in the superficial zone of rheumatoid cartilage suggests that immune complexes are deposited in the cartilage in this disease.
Arthritis Rheum
PMID:Electron microscopic demonstration of immunoglobulin deposition in rheumatoid cartilage. 5 68

Lymphocytes were eluted from synovial tissue of a boy with X-linked hypogammaglobulinemia and chronic polyarthritis. The cell suspension contained 53% lymphocytes and 28% peroxidase-positive, macrophagelike cells, No B lymphocytes, 83% T lymphocytes, and 10% Fc-receptor-bearing lymphocytes were detected. Lymphocyte transformation was induced by polyclonal mitogens (phytohemagglutinin and pokeweed mitogen) whereas no response to antigens (purified protein derivative and Candida albicans antigen) was obtained. The eluted cells displayed antibody-dependent cytotoxicity.
Arthritis Rheum 1979 Jan
PMID:Lymphocytes from synovial tissue of a boy with X-linked hypogammaglobulinemia and chronic polyarthritis. 36 88

By means of modelling arthritis by horseradish peroxidase it was possible to reproduce a process corresponding to immune synovitis. A considerable reduction of immunomorphological phenomena in joints, lymphoid tissue, heart, liver and kidneys was favoured by application of lymphoid tissue extracts. Comparison between the extracts of spleen and lymph nodes showed a more pronounced effect of spleen extract.
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PMID:Morphologic study of the action of lymphoid tissue extracts in peroxidase arthritis. 42 22

To determine the manner in which small protein antigens enter the synovium and are localized, horseradish peroxidase (molecular weight 40,000) was injected by intravenous and intraarticular routes. Passage of antigen from capillary lumen to joint space and vice versa occurred primarily across fenestrated vessels. Antigen localized to collagen fibers and lining cells. At low concentrations of antigen, antigen was taken up predominantly by marcophages, whereas at higher concentrations both macrophages and fibroblast-like lining cells accumulated antigen.
Arthritis Rheum
PMID:Fate of antigen after intravenous and intraarticular injection into rabbits. 73 15

The peroxidase activity is increased in the inflamed paw of rats with adjuvant arthritis. The increase is biphasic like for other enzymes. The higher peak occurs during primary inflammation in the injected paw according to the behaviour of polymorphonuclear leucocytes. Of 32 substances tested in vitro, among them 19 antiphlogistics and derivatives, especially the antiphlogistics inhibited the peroxidase reaction. Therfore it seems not unlikely that inhibition of the peroxidase reaction is involved in the mechanism of activity of anti-inflammatory agents.
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PMID:[Peroxidase activity in the paw of animals in adjuvant arthritis and its changes by antiphlogistics in vitro]. 113 98

We previously established that normal articular chondrocytes, like macrophages, express class II major histocompatibility antigens, present antigen, and induce mixed and autologous lymphocyte stimulation. In a recent study using the trapped indicator 2',7'-dichlorofluorescein diacetate, we were able to measure levels of intracellular hydrogen peroxide within normal articular chondrocytes (J Immunol 245:690-696, 1990). In the present study, we utilized the technique of chemiluminescence and the biochemical method of quantitating hydrogen peroxide release to measure the production of reactive oxygen intermediates by articular chondrocytes. Chondrocytes, in suspension or adherent to coverslips, showed luminol-dependent chemiluminescence that was dependent on the number and viability of cells. There was a dose-dependent increase in chemiluminescence in response to soluble stimuli, such as phorbol myristate acetate (PMA), concanavalin A (ConA), and f-Met-Leu-Phe (FMLP). Azide inhibited chemiluminescence, suggesting that the light emission in chondrocytes is myeloperoxidase dependent. The antioxidant, catalase, inhibited chemiluminescence but superoxide dismutase had no effect, suggesting that luminol-dependent chemiluminescence in chondrocytes mostly measured hydrogen peroxide. Chemiluminescence was also observed in fragments of live cartilage tissue, indicating that chondrocytes that are cartilage matrix bound can generate the respiratory burst response. Using the scopoletin oxidation assay, we confirmed the release of increasing amounts of hydrogen peroxide by chondrocytes exposed to interleukin-1, rabbit interferon, and tumor necrosis factor alpha. Tumor necrosis factor alpha had both priming and enhancing effects on reactive oxygen intermediate production by chondrocytes. Reactive oxygen intermediates have been shown to play a significant role in matrix degradation. We suggest that reactive oxygen intermediates produced by chondrocytes play an important role in the degradation of matrix in arthritis.
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PMID:Release of oxygen radicals by articular chondrocytes: a study of luminol-dependent chemiluminescence and hydrogen peroxide secretion. 128 Sep 2

Previous studies indicate that oxygen radical production by 1-min activation of N-formyl-methionyl-leucyl-phenylalanine-induced chemiluminescence (CL) by whole blood is increased in subjects with previous Yersinia arthritis (YA). This finding is confirmed in the present study and extended further by demonstrating that subjects with previous YA show increased oxygen radical generation and enhanced release of myeloperoxidase from neutrophils and increased CL activity by serum, all factors that can contribute to an increase in the initial activation of CL. Initial activation was not increased in subjects who had had Yersinia enteritis without arthritis; however, intracellular oxygen radical production by purified neutrophils was significantly increased, suggesting that the cells had been primed in vivo. The water-soluble antioxidants of plasma samples tested by a peroxyl radical-trapping assay were much the same in subjects with previous YA, in subjects with previous Yersinia enteritis without arthritis, and in healthy subjects. The results suggest that aberrations in neutrophil oxygen radical production play a role in the pathogenesis of YA.
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PMID:Oxygen radical production and trapping in subjects with previous Yersinia infection. 132 31

The purpose of this study was to assess the relationship of neuropeptide nerves and inflammatory leukocytes in PVG rats with adjuvant-induced arthritis. Substance P- and calcitonin gene-related peptide (CGRP)-immunoreactive nerves and inflammatory leukocytes were studied, using peroxidase (ABC) and/or alkaline phosphatase (APAAP) staining. Inflamed synovial tissue proper was infiltrated with neutrophils, ED1 macrophages and focal accumulations of CD2 T lymphocytes. In such tissue, the relationship between peptide-immunoreactive nerves and inflammatory cells was such that substance P and CGRP nerves were absent in heavily infiltrated villous synovial tissue, whereas healthy synovial tissue and non-inflammatory areas in adjuvant arthritic rats were innervated by substance P and CGRP nerves close to normal synovial tissue resident cells. In order to elucidate an eventual mechanism for lost immunoreactivity, healthy synovial tissue was exposed to chymotrypsin or oxygen derived free radicals (ODFR) in vitro. The former treatment caused total loss of immunoreactivity. These findings suggest that neuropeptides and neuropeptide containing nerves may be destroyed by locally produced proteolytic enzymes and various reactive oxygen species in the vicinity of inflammatory cells.
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PMID:Relationship between neuropeptide immunoreactive nerves and inflammatory cells in adjuvant arthritic rats. 137 4

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.
Semin Arthritis Rheum 1992 Aug
PMID:Collagenase in synovitis of rheumatoid arthritis. 141 81


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