Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.2.1.31 (beta-glucuronidase)
 7,680 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The contribution of activated oxygen species to neutrophil-mediated degradation of basement membrane collagen was investigated. In preliminary experiments, pre-exposure of either albumin or glomerular basement membrane to neutrophil myeloperoxidase with H2O2 and chloride increased their susceptibility to proteolysis 2-3-fold. In the basement membrane model, neutrophils are stimulated by trapped immune complexes to adhere, produce oxidants and degranulate. Degradation, measured as the amount of hydroxyproline solubilised, was due to neutral proteinases, particularly elastase, and depended on cell number and the amount of proteinase released. Experiments with oxidant scavengers and inhibitors and with neutrophils from donors with chronic granulomatous disease or myeloperoxidase deficiency showed that oxidants did not affect degradation of the basement membrane when this was measured on a per cell basis. However, oxidative inactivation of the released granule enzymes occurred. Activities of elastase, beta-glucuronidase and lysozyme were 1.5-2-times higher in the presence of catalase, but were unaffected by superoxide dismutase or hydroxyl radical scavengers. Inactivation did not occur with chronic granulomatous disease or myeloperoxidase deficient neutrophils. When related to the activity of released elastase, or to other degranulation markers, collagen degradation was decreased in the presence of catalase, or with chronic granulomatous disease or myeloperoxidase deficient cells. This implies that the basement membrane was made more digestible by myeloperoxidase-derived oxidants, as occurred in the cell-free experiments. Taken together, the results indicate that neutrophil oxidants have two opposing effects. They increase the susceptibility of the collagen to proteolysis and inactivate the proteinases responsible.
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PMID:The effect of oxidants on neutrophil-mediated degradation of glomerular basement membrane collagen. 302 26

Low density lipoprotein (LDL) isolated from sera of healthy volunteers in 50 micrograms protein/ml concentration induced an early adenylate cyclase activation in human monocytes followed by elevation of cGMP level. In addition, a rapid 45Ca2+ influx was also detected on addition of 25-100 micrograms protein/ml concentrations. The monocyte activating effect of LDL under in vitro circumstances was characterized by an enhanced O2 consumption, H2O2 generation and by the increased release of lysosomal enzymes such as beta-glucuronidase and elastase like protease (ELP). On the other hand, LDL diminished markedly the Fc gamma receptor (Fc gamma R) mediated rosette formation, phagocytosis and the antibody dependent cellular cytotoxicity (ADCC) of monocytes without a significant decrease in the IgG binding capability of cells. High levels of serum LDL may play a significant role in the arterial wall injury by elastase like protease as well as biologically active oxygen species released from monocytes of patients suffering from arteriosclerosis.
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PMID:Immunomodulating effect of low density lipoprotein on human monocytes. 302 82

Recombinant human tumour necrosis factor alpha (rHuTNF alpha) was shown to inhibit human neutrophil migration in the presence or absence of a chemotactic gradient generated with the tripeptide, N-formyl-L-methionyl-L-leucyl-L-phenylalanine (fMLP), at doses of 20-100 U/10(6) cells. In contrast, neither recombinant human interleukin-1 alpha (rHuIL-1 alpha), rHuIL-1 beta, human leucocyte-derived IL-1 alpha (1HuIL-1 alpha) nor 1HuIL-1 beta contained neutrophil migration inhibition properties. However, both the interleukins (1HuIL-1 alpha, 1HuIL-1 beta and rHuIL-1 alpha) and rHuTNF alpha stimulated a neutrophil respiratory burst and significantly elevated the neutrophil respiratory response to fMLP (measured as chemiluminescence and H2O2 production). The stimulatory effects were observed at doses of between 5 and 100 U/5 x 10(5) cells. A characteristic feature of the effects of the cytokines was the range of variation observed in neutrophil responses from different individuals. However, a concentration-related effect was observed with each experiment, delineating suboptimal, optimal and supra-optimal cytokine concentrations. Neutrophils treated with rHuTNF alpha and rHuIL-1 alpha and washed free of exogenous cytokine retained the capacity to show an enhanced response to fMLP. Pretreatment of cells with cytochalasin B enhanced their response to fMLP, and this response was further increased if the cells had also been pretreated with the cytokines. The response to phorbol myristate acetate was also enhanced by rHuTNF alpha and rHuIL-1 alpha. The effects of these cytokines on neutrophils could be abolished by boiling the preparation but not by treating it with polymixin B, suggesting that bacterial lipopolysaccharide was not responsible for the activity of these preparations. The rHuIL-1 alpha increased the release of lysozyme, beta-glucuronidase and myeloperoxidase initiated by cytochalasin B/fMLP, while rHuTNF alpha only increased lysozyme release.
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PMID:Effects of tumour necrosis factor alpha and interleukin-1 alpha and beta on human neutrophil migration, respiratory burst and degranulation. 328 22

Culture medium conditioned by mononuclear leucocytes (MNL) stimulated by formalin-fixed heat-killed Staphylococcus aureus (sCM) modulated a number of neutrophil functions. The sCM inhibited the locomotion of human neutrophils in both the presence and absence of a chemotactic gradient generated with N-formyl-L-methionyl-L-leucyl-L-phenylalanine (FMLP). It also stimulated the oxygen-dependent respiratory burst as assessed by its ability to stimulate basal H2O2, superoxide and chemiluminescence production by neutrophils. Neutrophils treated with sCM also showed increased release of lysozyme but not beta-glucuronidase. In addition, the sCM-treated neutrophils showed a potentiated response to stimuli that bind surface receptors, i.e. FMLP and opsonized zymosan. The effects of sCM and either of the stimuli were synergistic. Examination of lysosomal enzyme release showed that sCM enhanced the release of lysozyme and beta-glucuronidase induced by either FMLP/cytochalasin B or zymosan. The response to phorbol myristate acetate (PMA), which bypasses the surface receptor, was also stimulated but compared poorly with the FMLP response. The sCM effects on the FMLP-induced chemiluminescence response occurred even when FMLP addition was delayed for 4 hr. Cells treated with sCM and washed retained the ability to show an enhanced FMLP response. The neutrophil-modulating activity was not produced by MNL cultured in the absence of bacteria.
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PMID:Staphylococcus aureus-stimulated human mononuclear leucocyte-conditioned medium augments the basal and stimuli-induced neutrophil respiratory burst and degranulation. 357 Mar 57

Human colostral macrophages stimulated by opsonized zymosan or phorbol myristate acetate (PMA) released superoxide anions (O2-) and hydrogen peroxide (H2O2) with activities comparable to those of monocytes and about one-fourth of those of polymorphonuclear leukocytes (PMNL) of blood. The O2- -forming oxidase in the macrophages stimulated by PMA was dependent on NADPH as an electron donor with an apparent Km value for NADPH of 27.6 +/- 4.0 microM, which is comparable to those obtained for the stimulated monocytes and PMNL of blood. The Vmax was 1.86 +/- 0.33 nmol O2/min/10(6) cells, which is essentially the same as that of monocytes and about half of that of PMNL. p-Chloromercuribenzoate or cetyltrimethylammonium bromide completely inhibited oxidases of all three types of phagocytes. A b-type cytochrome was identified in the macrophages but the concentrations in the macrophages and monocytes were less than half of that in PMNL. These results suggest that the differences in the O2- -forming activities of the three types of phagocytes are quantitative rather than qualitative. The macrophages and monocytes showed very low activities of myeloperoxidase [EC 1.11.1.7] in contrast to PMNL. The activity of beta-glucuronidase [EC 3.2.1.31] in the macrophages was much higher than those of the monocytes and PMNL, but little difference was observed in the activities of lysozyme [EC 3.2.1.17], catalase [EC 1.11.1.6] and superoxide dismutase [EC 1.15.1.1] among the three types of phagocytes examined. Electron micrographs of the macrophages showed little increase of vacuoles upon exposure to PMA, in contrast to the cases of monocytes and PMNL.
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PMID:Oxygen metabolism of human colostral macrophages: comparison with monocytes and polymorphonuclear leukocytes. 608

A number of cytochemical parameters of the hemocytes of larval Galleria mellonella, an insect frequently used as a model by comparative cellular immunologists, are described. Cytochemical methods were used to quantify hemocyte granule-associated components, the results are compared to those obtained for leukocytes from higher animals. Granulocytes contained a population of nonlysosomal granules rich in mucopolysaccharide not seen in plasmatocytes. The numbers and dimensions of these granules showed a positive correlation to cell size, probably reflecting a developmental sequence in granulocyte maturation. Both granulocytes and plasmatocytes had other granules containing the typical lysosomal enzymes, acid phosphatase, beta-glucuronidase, esterase, and lysozyme. The nonlysosomal enzyme alkaline phosphatase was not found in Galleria hemocytes; it is also absent from vertebrate monocytes, macrophages, and immature polymorphonuclear leukocytes. Insect hemocytes appear to lack certain components of antibacterial systems typical of mammalian blood cells, such as H2O2-generating systems, cationic proteins, and myeloperoxidase. The bactericidal mechanisms of hemocytes probably involve lysozyme, as well as other biologically active cellular and humoral factors unique to insects.
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PMID:Observations on the cytochemistry of the hemocytes of an insect, Galleria mellonella. 618 80

Enzymatic equipment in peripheral blood neutrophils has been determined in 10 women with cervical carcinoma, 5 with carcinoma of the uterus body and 30 women with myomas of the uterus. Using cytochemical techniques the authors observed the intracellular deficiency of N-acetyl-beta-glucosaminidase accompanied by diminished absolute count of the enzyme-positive cells as well as the beta-glucuronidase- and the myeloperoxidase-positive neutrophils. Lowered activity of the myeloperoxidase was another pattern of cells in question. The acid phosphatase activity of neutrophils in the patients was significantly elevated. It has been suggested that observed intracellular deficiencies of selected enzymes within the neutrophils are of importance with regard to lowered antitumor activity of that cells operating mainly through the myeloperoxidase-H2O2-halide system.
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PMID:Enzymes of neutrophils in women with malignant tumors of reproductive organs. 625 27

The role of glutathione peroxidase (GSH-Px) in protecting phagocytic function of peritoneal granulocytes (PMN) was assessed using selenium (Se)-deficient rats. Rats fed an Se-deficient diet for 12-15 weeks developed profound Se deficiency. Their PMN were found to contain 11% of control levels of GSH-Px. Previous studies have shown that at this level of enzyme activity, the metabolism of H2O2 via the glutathione cycle was impaired. Despite this, the initial rate of phagocytosis, as measured by the ingestion of opsonized oil red O particles, was normal. Prior incubation of PMN in an H2O2-generating system resulted in a time-dependent loss in the ability of the cells to ingest. GSH-Px-deficient PMN were affected to a greater degree than control PMN. Degranulation, as measured by the release of beta-glucuronidase into the extracellular medium after stimulation of PMN by opsonized zymosan in the presence of cytochalasin B, was unaffected by GSH-Px deficiency. Prior incubation of PMN in an H2O2 generating system resulted in decreased degranulation in both control and GSH-Px-deficient PMN, with GSH-Px-deficient PMN being affected to a greater degree. The killing of Staphylococcus aureus 502A by both control and GSH-Px-deficient PMN was the same. There was no effect of prior H2O2 incubation on bacterial killing in either control or GSH-Px-deficient PMN. Thus, GSH-Px appears to be important in protecting those aspects of phagocytic function that are sensitive to the destructive properties of exogenous H2O2.
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PMID:Increased sensitivity to H2O2 in glutathione peroxidase-deficient rat granulocytes. 649 56

Neutrophils from the synovial fluid (SFN) of 10 patients with active rheumatoid arthritis (RA) were investigated to determine the generation of oxygen intermediates (OI) (O2-, H2O2, OH .), chemiluminescence, and lysosomal enzymes (lysozyme and beta-glucuronidase). Lymphocytes from healthy individuals were cocultured at 37 degrees C for 17 hr with SFN from the patients and the number of OKT4+, OKT8+, and OKT3+ cells and the response to mitogens were determined. A markedly increased OI and slightly elevated lysosomal enzyme levels were observed in SFN from patients. Coculture of lymphocytes with SFN resulted in a decreased number of OKT4+ and OKT8+ cells and a greatly reduced response to Con A and mildly diminished response to PHA, while OKT3+ cells were not affected. The simultaneous addition of superoxide dismutase and catalase restored the impairment of monoclonal antibody reaction and lymphocyte responsiveness almost to control levels. It is suggested that the disturbed immunoreactivity of synovial fluid lymphocytes from RA patients may be due to increased OI generated by stimulated neutrophils.
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PMID:Effect of stimulated neutrophils from the synovial fluid of patients with rheumatoid arthritis on lymphocytes--a possible role of increased oxygen radicals generated by the neutrophils. 660 65

The influence of a selenium deficient diet in mice and rats has been studied on glutathione peroxidase (GSH-Px) and secretory activities of peritoneal macrophages, mitogenesis of spleen cells and adjuvant arthritis. Macrophage GSH-Px activity was significantly reduced from 9 weeks on the selenium deficient diet. This reduction was associated with enhanced macrophage H2O2 release on zymosan stimulation after 12 weeks on the diet, a similar trend in chemiluminescence and reduced mitogenesis of spleen cell cultures to T and B cell mitogens after 8 weeks on the diet. Macrophage beta-glucuronidase release was not significantly altered. Phorbol myristic acetate induced macrophage H2O2 generation was reduced by selenium deficiency, possibly due to increased cellular damage. Adjuvant arthritis of rats was significantly enhanced after 6 and 12 weeks on the selenium deficient diet. The enhanced release of H2O2 by macrophages after zymosan stimulation can be directly attributable to loss of GSH-Px activity leading to reduced peroxide breakdown. Peroxide-mediated cell injury would also account for the reduction in lymphocyte mitogenesis and enhancement of adjuvant arthritis. These data provide support for a role of selenium in immune and inflammatory responses.
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PMID:Macrophage, lymphocyte and chronic inflammatory responses in selenium deficient rodents. Association with decreased glutathione peroxidase activity. 665 41


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