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:1.11.1.7 (peroxidase)
65,474 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Microbiostatic mechanisms may contribute substantially to host defense against infection by certain microbes. We studied the candidastatic activity of human neutrophils, neutrophil cytosol, and neutrophil-derived "calprotectin," a cytosolic protein complex comprised of two subunits, MRP8 and MRP14. Intact neutrophils, neutrophil lysates (prepared by ultrasonic disruption, freezing and thawing, or nonionic detergent extraction), and granule-depleted neutrophil cytosol were effective in restricting the growth of Candida albicans in a nutrient-rich tissue culture medium, RPMI 1640. Neither a subcellular fraction enriched in neutrophil granules nor selected purified granule components (lactoferrin, myeloperoxidase, cathepsin G, leukocyte elastase, lysozyme, and defensins) exerted candidastatic activity in this medium. Gel filtration liquid chromatography, anion exchange FPLC, and SDS-PAGE showed that the fungistatic factor in neutrophil cytosol was associated with the calprotectin complex. Its antifungal effects included restriction of yeast phase and mycelial growth and inhibition of glucose incorporation by yeast phase cultures. The antifungal effects of calprotectin were sustained for over 120 h and were inhibited by zinc. However, studies with 65Zn-enriched RPMI suggested that the candidastatic effects of calprotectin were not mediated by sequestration or binding of zinc. After reversed phase HPLC, calprotectin fractions containing MRP14 exhibited fungistatic activity, whereas fractions depleted of MRP14 but enriched for MRP8 lacked fungistatic activity. The results support a potentially significant role for the calprotectin complex of neutrophil cytosol in antifungal defense and suggest that MRP14 is of key importance in that activity.
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PMID:In vitro candidastatic properties of the human neutrophil calprotectin complex. 824 68

The human polymorphonuclear leukocyte reaction in response to chemotactic or chemokinetic stimulation is often assayed using the Boyden chamber technique. We present a quick and reliable method for evaluating Boyden chamber experiments, which avoids time-consuming cell counting and does not require expensive equipment. This method is based on assaying human neutrophil elastase, a serine protease derived from polymorphonuclear leukocytes. We tested the method in different types of Boyden chambers equipped with two superimposed filters or a filter amnion membrane combination. The chambers were incubated with the cells for 2 h then dismantled and the elastase activity in supernatant, filters or membrane was assayed. The results were compared with the results obtained by cell counting, or measured by determination of myeloperoxidase. There was a good correlation between the cell count and elastase technique (r = 0.90), but the elastase method achieved higher intra- and interassay precision. Myeloperoxidase and elastase results also correlated well (r = 0.94) and showed comparable intra- and inter-assay precision. With the elastase method it was also possible to quantify polymorphonuclear leukocyte reactions on an amnion membrane surface. In amnion membrane assays the percentage of cells which reacted in response to formyl-peptide stimulation was not altered by varied cell concentrations, and polymorphonuclear leukocytes showed little unstimulated adherence or migration.
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PMID:Granulocyte chemotaxis measured in a Boyden chamber assay by quantification of neutrophil elastase. 829 66

Proteolytic enzymes derived from inflammatory cells or Pseudomonas aeruginosa may destroy lung matrix in cystic fibrosis (CF). Antielastases appear to be overwhelmed by large amounts of free neutrophil elastase (NE) activity in lower respiratory tract secretions, and proteolytic or oxidant stress is thought to account for such deficiency. The purpose of this study was to measure NE and myeloperoxidase activity in bronchoalveolar lavage fluid (BAL) from patients with CF and to correlate levels of these mediators with the degree of airflow obstruction and density of P. aeruginosa in BAL. We measured NE activity in BAL fluid from 14 patients with respiratory exacerbations of CF. NE complexed with alpha 1-antiprotease in peripheral blood was measured in 13 of the 14 patients subjected to BAL and in 21 additional patients who did not undergo BAL. Because oxidants generated by myeloperoxidase may contribute to increased elastase activity via inactivation of alpha 1-antiprotease, myeloperoxidase activity in BAL was also measured. We found that elastase activity in BAL correlated significantly with the ratio of forced expiratory volume in 1 second to forced vital capacity (FEV1/FVC ratio) (r = -0.80, p < 0.001) and FEV1 percent predicted (r = -0.62, p = 0.02). Myeloperoxidase activity also significantly correlated with airflow obstruction (FEV1/FVC ratio, r = -0.70, p = 0.005; FEV1 percent predicted, r = -0.52, p = 0.05). However, the degree of airflow obstruction, NE activity, myeloperoxidase activity, or total neutrophils in BAL did not correlate with the density of P. aeruginosa (CFU/ml) or total pathogen burden in BAL fluid.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Neutrophil mediators, Pseudomonas, and pulmonary dysfunction in cystic fibrosis. 847 90

The aim of this study was to evaluate the ability of alveolar inflammatory cells recovered by bronchoalveolar lavage from the lower respiratory tract of 17 smoking patients with or without emphysema to inactivate alpha 1-proteinase inhibitor (alpha 1-Pl). The presence of emphysema was determined and quantified using CT scan and was evidenced in 8 patients (Group 1), whereas 9 patients exhibited a normal CT scan (Group 2). Patients with emphysema had lower values of FEV1, DLCO, and resting PO2 and higher values of RV/TLC ratio than patients without emphysema. BAL analysis showed a higher percentage of neutrophils and of myeloperoxidase (MPO) in BAL fluid in Group 1 than in Group 2. Alveolar inflammatory cells stimulated or not with phorbol myristate acetate (PMA) were incubated for 45 min with purified alpha 1-Pl, and the results were expressed as a percentage of inactivation of alpha 1-Pl as evaluated by its inhibitory activity against porcine pancreatic elastase or human neutrophil elastase. In Group 2, unstimulated alveolar inflammatory cells inactivated only 3.3 +/- 0.7% alpha 1-Pl and stimulated cells inactivated only 5.4 +/- 1.1% alpha 1-Pl. In marked contrast, in Group 1, a significant loss of the antielastase function of alpha 1-Pl was observed (p < 0.001) when alpha 1-Pl was incubated with unstimulated cells (24.2 +/- 8.9%) or stimulated cells (35 +/- 8.9%) from Group 1. The addition of catalase to the cell suspension was associated with a significant decrease in the inactivation of alpha 1-Pl (from 35 +/- 8.9 to 10.2 +/- 1.2%, Group 1).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Inactivation of alpha 1-proteinase inhibitor by alveolar inflammatory cells from smoking patients with or without emphysema. 838 10

The degradation of the heparan sulfate proteoglycans of subendothelial matrix by neutrophil elastase and the myeloperoxidase-H2O2-chloride system added separately, sequentially, or together at pH 4.5 to 7.5 was determined by the release of lower molecular weight 35S-labeled material. Elastase alone and the myeloperoxidase system alone caused degradation, and when 4-hour exposure to elastase was followed by 15 minutes of exposure to the myeloperoxidase system, the effect was greater than additive. A greater than additive effect was not observed when elastase followed the myeloperoxidase system or the two were added together. Chloride (or sulfate) alone increased the release of 35S-labeled material from elastase-treated matrix, although the effect of 0.1 M chloride was not as great as that observed when an equivalent concentration of chloride was combined with myeloperoxidase and H2O2. The release of these systems at sites of adherence of neutrophils to glomerular basement membrane may contribute to neutrophil-associated proteinuria.
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PMID:Degradation of endothelial cell matrix heparan sulfate proteoglycan by elastase and the myeloperoxidase-H2O2-chloride system. 839 74

Recently it has been demonstrated that human antibody fragments with binding activities against self antigens can be isolated from repertoires of rearranged V genes from non-immunized humans. We have applied phage display technology to study the B cell repertoire for antibody activity against neutrophil cytoplasmic antigens. These antibodies may play an important role in Wegener's granulomatosis (WG) and related forms of vasculitides. Autoantibodies in patients with WG are directed against proteinase 3. The immunodominant antigen in other forms of vasculitis is myeloperoxidase, but the B cell response can also be directed against other neutrophil enzymes, e.g. lysozyme, human neutrophil elastase, lactoferrin and cathepsin G. We show here that anti-self reactivity against neutrophil cytoplasmic antigens can be detected in the rearranged V gene repertoire of healthy individuals and that the reactivity can be directed against structural related epitopes which are present on different neutrophil cytoplasmic antigens. The scFv with binding activities were sequenced and the V gene usage, the level of somatic mutations and the immunoserological characteristics of the antibody fragments are discussed. Further evidence is presented that antibody fragments consisting only of a heavy chain variable domain can recognize neutrophil cytoplasmic antigens in a specific manner. These single-domain antibody fragments were used in experiments designed to establish the relative role of the light chain variable domains in antigen binding.
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PMID:Molecular characteristics of anti-self antibody fragments against neutrophil cytoplasmic antigens from human V gene phage display libraries. 853 74

We investigated the effect of activated protein C (APC) on lipopolysaccharide (LPS)-induced pulmonary vascular injury in rats to investigate the possible usefulness of APC as a treatment for adult respiratory distress syndrome. Intravenously administered LPS (5 mg/kg) significantly increased pulmonary vascular permeability. APC prevented the LPS-induced increase in pulmonary vascular permeability observed at 6 hours. Heparin plus antithrombin III (ATIII) and active site-blocked factor Xa (DEGR-Xa), a selective inhibitor of thrombin generation, inhibited LPS-induced coagulopathy but did not prevent LPS-induced pulmonary vascular injury. LPS-induced pulmonary vascular injury was significantly attenuated in rats with nitrogen mustard-induced leukocytopenia and in rats treated with ONO-5046, a potent granulocyte elastase inhibitor. Administration of LPS also increased pulmonary accumulation of leukocytes, as evaluated by measurement of myeloperoxidase activity in the lungs. APC significantly reduced LPS-induced increases in pulmonary accumulation of leukocytes at 1 hour. Neither ATIII plus heparin nor DEGR-Xa inhibited leukocyte accumulation. Active site-blocked APC (DIP-APC) prevented neither the LPS-induced pulmonary accumulation of leukocytes nor the LPS-induced increase in pulmonary vascular permeability. These results suggest that the mechanism of APC inhibition of LPS-induced pulmonary vascular injury was independent of its anticoagulant activity and was related to its ability to inhibit accumulation of leukocytes. In addition, these findings suggest that the serine protease activity of APC may be essential to its inhibitory effect on LPS-induced pulmonary accumulation of leukocytes and subsequent pulmonary vascular injury.
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PMID:Activated protein C attenuates endotoxin-induced pulmonary vascular injury by inhibiting activated leukocytes in rats. 855 86

The effects of fluticasone propionate (FP) on sputum chemotactic activity, elastase inhibitory potential, albumin concentrations, and peripheral neutrophil function were studied in a group of patients with clinically stable, smoking-related chronic bronchitis and emphysema. Seventeen patients (50 to 75 yr of age) were entered into a double-blind, placebo-controlled study of 1.5 mg inhaled FP/d for 8 wk. Following treatment with FP the chemotactic activity of the sputum sol phase was lower than the corresponding values for the placebo group (p < 0.01). Values fell from a mean of 21.75 (+/- 1.58) during the run-in period to 18.37 (+/- 1.46; p < 0.01) after 4 wk and 17.63 (+/- 1.86; p < 0.05) after 8 wk treatment returning to 22.08 (+/- 1.26) cell/field after the washout period. The neutrophil elastase inhibitory capacity of the sputum sol phase increased (p < 0.025) with treatment from a mean of 0.177 microM elastase inhibited/L (+/- 0.05) pretreatment to 0.413 microM (+/- 0.054) after 4 wk and 0.415 microM (+/- 0.054) after 8 wk returning to 0.270 microM (+/- 0.07) after the washout period. Treatment with FP did not result in a change in the peripheral neutrophil functions studied or sputum albumin and myeloperoxidase concentrations. The results suggest that FP may play a protective role in these patients through a reduction in the chemotactic activity of lung secretions and potentially a reduction in the recruitment of neutrophils to the lung, and also by directly affecting the proteinase/antiproteinase balance, in favor of antiproteinases, within lung secretions.
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PMID:Effect of fluticasone propionate on sputum of patients with chronic bronchitis and emphysema. 856 7

Hairless (SKH-1) mice were mated with beige (C57BL/bb) mice to produce a hairless mouse deficient in neutrophil elastase (hhbb). These mice were exposed to 0.09 J UVB radiation for 5 months to see if neutrophil elastase was an important factor in the development of solar elastosis. Analysis of peritoneal neutrophils confirmed that the hhbb mouse was deficient in elastase, retaining only 10% of the activity of the normal littermates (hhHb). Skin myeloperoxidase activity was equally elevated in all the mice receiving UVB indicating a similar influx of inflammatory cells. The absolute breaking strength of the skin in both the hhBb and hhbb mice was not altered by UVB treatment over the 5 month exposure period. Elastin quantitated biochemically as desmosine, or visualized histologically, was increased following UVB exposure in the normal mice. In the elastase-deficient mice, however, the elastin fibres appeared to be unaffected by exposure to UVB radiation at this level. The results suggest that neutrophil elastase is an important mediator in the development of solar elastosis resulting from continued exposure to UVB.
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PMID:A role for neutrophil elastase in solar elastosis. 857 66

Bronchiectasis is associated with sputum containing high levels of the proteolytic enzyme elastase, which is thought to be involved in the pathogenesis of the disease. Agents which inhibit neutrophil function and interfere with neutrophil elastase release may have a beneficial effect on the development and progression of such diseases. We have studied the effects of the nonsteroidal anti-inflammatory agent indomethacin on neutrophil function in nine patients with clinically stable bronchiectasis. All patients remained clinically stable during the study. We observed a significant reduction in peripheral neutrophil chemotaxis to 10 nmol.L-1 N-formyl-methionyl-leucyl-phenylalanine (FMLP) from a mean of 19.86 (SEM 1.35) to 8.46 (0.68) cells.field-1 after 4 weeks of therapy. There was also a significant reduction in fibronectin degradation both by resting and FMLP-stimulated neutrophils, from a mean of 1.90 (0.19) micrograms x 3 x 10(5) cells at the start of therapy to 0.87 (0.08) micrograms after 4 weeks, and from 3.17 (0.35) micrograms to 1.48 (0.05) micrograms, respectively. There was no effect on spontaneous or stimulated superoxide anion generation by neutrophils. Despite the marked changes in peripheral neutrophil function, no adverse effect was observed on viable bacterial load in the bronchial secretions. In addition, there was no difference in sputum albumin, elastase or myeloperoxidase levels, and only minor changes in the chemotactic activity of the sputum. These results suggest that nonsteroidal anti-inflammatory agents have a major effect on peripheral neutrophil function but do not appear to have an adverse effect on bacterial colonization of the airways.
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PMID:In vivo study of indomethacin in bronchiectasis: effect on neutrophil function and lung secretion. 857 72


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