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)

The neutrophil myeloperoxidase-H2O2-halide enzyme system produces hypochlorous acid and chlorinated amine compounds capable of killing a variety of target cells. In the present study we hypothesized that the myeloperoxidase enzyme system is one mechanism for airway epithelial damage in patients with cystic fibrosis (CF). Enzyme linked immunosorbent assay detected high antigenic levels of myeloperoxidase in sputum samples of seven patients with CF. Myeloperoxidase was purified to homogeneity from CF sputum and from blood neutrophils by a three-step technique involving dialysis, gel filtration, and ion-exchange chromatography. CF sputum myeloperoxidase and neutrophil myeloperoxidase appeared identical by acid gel electrophoresis and Ouchterlony experiments. CF sputum myeloperoxidase also contained approximately the same enzymatic activity as neutrophil myeloperoxidase. The myeloperoxidase enzyme system was tested for its cytotoxic potential in a tracheal ring culture system. Myeloperoxidase-induced cytotoxicity for airway epithelium was confirmed by light microscopy and radiolabelling experiments. These findings suggest a possible role for neutrophil myeloperoxidase in CF lung disease.
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PMID:Purification and cytotoxic potential of myeloperoxidase in cystic fibrosis sputum. 284 83

Cigarette smokers have an increased risk of chronic obstructive airways disease which has been attributed to a protease-antiprotease imbalance in the lung. The neutrophil is an important source of proteases as well as of myeloperoxidase, which oxidatively inactivates alpha-1-proteinase inhibitor (alpha-1-PI). The purpose of this study is to evaluate the protease-antiprotease imbalance hypothesis by measuring changes in peripheral blood components in a group of 110 young, male, asymptomatic smokers and an equal number of age-matched non-smokers. Significant (p = 0.001), but modest impairment of pulmonary function was observed in the smokers as measured by both forced expiratory spirometry and the single breath nitrogen test. A 35% increase (p = 0.0001) in peripheral blood leukocytes in smokers was attributable to increases in neutrophils (44%), lymphocytes (31%) and monocytes (23%). This increase in leukocyte count correlated significantly (p less than or equal to 0.01) with some of the more sensitive indicators of airway obstruction (FEV1/FVC, CV/VC, CC/TLC, and delta N2/L). Myeloperoxidase activity of neutrophils isolated from peripheral blood of smokers was 13% higher than in non-smokers, while elastase activity per neutrophil was apparently unaffected by smoking. In 50 subject pairs, elevations in serum alpha-1-PI concentrations in smokers (13.7%) were comparable to similar increases in trypsin (9.9%) and elastase (12.4%) inhibitory capacities. Expressed as nanomoles protease inhibited per nanomole of alpha-1-PI, the apparent functional activity of alpha-1-PI was unaltered by smoking. However, a lower, apparent functional activity of alpha-1-PI against trypsin and elastase was observed in both smokers and non-smokers with higher serum alpha-1-PI concentrations. Thus, in a population of young smokers, changes in leukocyte count, neutrophil lysosomal enzyme activities, and functional serum antiprotease activity appear to be consistent with the establishment of a protease-antiprotease imbalance. This imbalance may predispose these smokers to obstructive lung disease.
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PMID:Effect of smoking on peripheral blood leukocytes and serum antiproteases. 299 5

Activated granulocytes have been implicated in mediating pulmonary endothelial damage in the Adult Respiratory Distress Syndrome. In another lung disease, emphysema, pulmonary granulocytes (PMNs) are thought to be doubly responsible for lung dissolution: they release potent proteolytic enzymes including elastase, and they generate reactive oxygen species that oxidize a reactive site methionine group in alpha-1-protease inhibitor (alpha-1-PI) rendering it, in turn, impotent as an anti-elastase. This suggested an analogous scenario for pulmonary vascular damage: namely, undefended PMN elastase might also mediate endothelial injury. Our strategy to prove this notion used 51chromium-labeled human endothelial cells exposed to intact PMN or to enucleate "neutroplasts." The latter are elastase-free cytoplasmic blebs derived from PMN. When activated, both PMN and neutroplasts generate similar amounts of toxic oxygen species; yet neutroplasts caused insignificant endothelial damage, measured as 51Cr "lift-off"from anchoring matrix (PMN = 24.3% +/- 1.8% vs neutroplast = 1.2% +/- 0.4%; p less than 0.001). Adding pure elastase back to neutroplasts increased endothelial cell lift-off (7% +/- 0.2%). Although the prototypic serine protease inhibitor phenyl methylsulfonylfluoride (PMSF) protected endothelium from PMNs, pure alpha-1-PI (also a potent anti-elastase) when added in physiologic amounts did not protect endothelial cells from PMN assault, suggesting that PMN oxidants might inactivate it. By adding exogenous myeloperoxidase (MPO) to MPO-deficient neutroplasts, we demonstrated that MPO-dependent oxidants, probably N-chloramines, are critical inactivators of alpha-1-PI. This was further confirmed since added free methionine, a scavenger of chloramine, protected alpha-1-PI from inactivation by reagent chloramine or that produced by rearmed neutroplasts or PMN.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Neutrophil oxidants inactivate alpha-1-protease inhibitor and promote PMN-mediated detachment of cultured endothelium. Protection by free methionine. 348 53

Immunocytochemistry using horseradish peroxidase-antiperoxidase technique was performed on the lungs of 60 human fetuses and newborn infants of 8 to 40 weeks' gestation and from birth to 7 months' postnatal life. Tissue was stained for the peptide hormones, immunoreactive (IR) bombesin, IR calcitonin and IR Leu-enkephalin, as well as for IR serotonin. IR bombesin appeared in neuroendocrine cells and neuroepithelial bodies in the developing conducting airways of fetuses by 10 weeks' gestation and increased in number primarily in bronchioles as gestation progressed. They were most numerous in live-born infants with chronic respirator lung disease. In contrast, IR calcitonin-staining cells did not appear until late in the second trimester. They were present in small numbers from 20 weeks onward but were also most numerous in infants with chronic respirator lung disease. IR serotonin-staining cells were readily found in lungs of fetuses in the first trimester. By the second trimester many solitary neuroendocrine cells and neuroepithelial bodies staining for IR serotonin were present in developing terminal airways and a lesser number appeared in bronchioles and intrapulmonary bronchi. In premature infants, IR serotonin-staining cells were scarce in the presence of acute hyaline membrane disease but were numerous in lungs of infants with regenerating conducting airways associated with chronic respirator lung disease. IR Leu-enkephalin-staining cells were found only in one infant who survived 7 postnatal months of respirator care following neonatal hyaline membrane disease.
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PMID:Ontogeny of neuroendocrine cells in human fetal lung. II. An immunohistochemical study. 388 Aug 41

Chronic obstructive pulmonary disease (COPD), a major cause of morbidity and death in the smoking population, develops insidiously over many years, and significant impairment of lung function usually occurs before the disease is diagnosed. Because lung elastin degradation appears to be a prerequisite for the development of the disease, immunologic detection of elastin-derived peptides in the blood might be an effective approach to the early detection and monitoring of the disease. We here report an improved enzyme-linked immunosorbent assay for elastin peptides using a peroxidase-antiperoxidase complex as the reporter group. The assay is sensitive to 2 ng/ml elastin peptides. We show that for optimal, reproducible results the assay should be carried out at 16 degrees C rather than at room temperature and that determinations should be made on plasma containing protease inhibitors rather than on serum. The levels of elastin-derived peptides appeared to remain relatively constant when multiple samples were taken during a 5- to 10-wk period from individual subjects. In addition, patients with COPD had elevated elastin peptide levels (127 +/- 47 ng/ml) compared with levels in normal nonsmokers (58 +/- 17 ng/ml), whereas normal smokers had values intermediate between the 2 groups (mean peptide levels of 76 +/- 42 ng/ml). A small group of normal smokers (20%) had elevated elastin peptide levels similar to those in the emphysema group and may represent that group of smokers who are at risk of developing obstructive lung disease.
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PMID:Utilization of a peroxidase antiperoxidase complex in an enzyme-linked immunosorbent assay of elastin-derived peptides in human plasma. 389 Jun 38

Freshly prepared aqueous solutions of cigarette smoke suppressed the elastase inhibitory capacity (EIC) of the acid-stable proteinase inhibitor present in bronchial mucus (BMPi) and human seminal plasma (HUSI-I). Thin-layer gel-immunofiltration analysis of mixtures of smoke-treated BMPi and human leukocyte elastase showed decreased elastase: BMPi complexes, increased uncomplexed BMPi and increased free elastase. Phenolic antioxidants prevented the suppression of the EIC of BMPi or HUSI-I by cigarette smoke. In addition, treatment of BMPi or HUSI-I with chemical oxidants caused a similar suppression of EIC. Furthermore, treatment of BMPi or HUSI-I with the phagocyte-derived oxidizing system, myeloperoxidase + H2O2 + Cl-, suppressed EIC. Finally, the functional activity of BMPi was significantly reduced in tracheal aspirates of human smokers compared to that of nonsmokers. These results support the hypothesis that local inactivation of BMPi in the conducting airways of the lung by inhaled cigarette smoke or by phagocyte-derived oxidants may play a role in the pathogenesis of obstructive lung disease in smokers.
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PMID:Inactivation of bronchial mucous proteinase inhibitor by cigarette smoke and phagocyte-derived oxidants. 701 95

Anti-neutrophil cytoplasmic autoantibodies (ANCA) occur in a subset of patients with systemic small vessel vasculitis, including patients with Wegener's granulomatosis, microscopic polyangiitis (microscopic polyarteritis), and Churg-Strauss syndrome. Pulmonary disease appears at some time during the course in many patients with ANCA-associated vasculitis. The histologic features of 25 open lung biopsies and two autopsy cases were studied from 27 patients with ANCA. Patients' ages ranged from 8 to 79 years with a mean of 52.6 years. There were 12 females and 15 males. Autoantibodies were characterized as C-ANCA in 13 patients and as P-ANCA in 14 patients. Anti-proteinase 3 antibodies were documented in 12 of 13 patients with C-ANCA. Anti-myeloperoxidase antibodies were documented in all 14 patients with P-ANCA. Vascular lesions were present in 21 patients (78%) and 11 patients (41%) had bronchial lesions. Capillaritis was the most common vascular lesion (17 patients, 63%), and was found with similar frequency in patients with C-ANCA and those with P-ANCA. Extravascular structures were a common site of tissue injury. Airway lesions including bronchiolitis obliterans organizing pneumonia (4 patients, 19%), necrotizing granulomatous inflammation (4 patients, 15%), and non-granulomatous inflammation (3 patients, 11%) were more commonly associated with patients with C-ANCA. Interstitial lesions were found in 20 patients (74%), and included necrotizing granulomatous inflammation (8 patients, 30%), fibrosis (13 patients, 48%), and chronic inflammation (12 patients, 44%). No histologic lesion were found that were specific for C-ANCA or P-ANCA. This series demonstrates the wide variety of pulmonary lesions found in patients with ANCA-associated pulmonary disease, and shows that extravascular structures are a common site of injury in ANCA-associated vasculitis.
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PMID:The pathologic spectrum of pulmonary lesions in patients with anti-neutrophil cytoplasmic autoantibodies specific for anti-proteinase 3 and anti-myeloperoxidase. 761 Nov 70

Oxidant-mediated toxicity resulting from acute pulmonary inflammation has been demonstrated in acute lung injury. A potent biological oxidant, peroxynitrite, is formed by the near diffusion-limited reaction of nitric oxide with superoxide. In addition to having hydroxyl radical-like oxidative reactivity, peroxynitrite is capable of nitrating phenolic rings, including protein-associated tyrosine residues. Nitric oxide does not directly nitrate tyrosine residues, therefore, demonstration of tissue nitrotyrosine residues infers the action of peroxynitrite or related nitrogen-centered oxidants. Lung tissue was obtained from formalin-fixed, paraffin-embedded autopsy specimens, and specific polyclonal and monoclonal antibodies to nitrotyrosine were visualized by diaminobenzidene-peroxidase staining. Acute lung injury resulted in intense staining throughout the lung, including lung interstitium, alveolar epithelium, proteinaceous alveolar exudate, and inflammatory cells. In addition, staining of the vascular endothelium and subendothelial tissues was present in those patients with sepsis-induced acute lung injury. Antibody binding was blocked by coincubation with nitrotyrosine or nitrated bovine serum albumin but not by aminotyrosine, phosphotyrosine, or bovine serum albumin. Reduction of tissue nitrotyrosine to aminotyrosine by sodium hydrosulfite also blocked antibody binding. In control specimens with no overt pulmonary disease, there was only slight staining of the alveolar septum. These results demonstrate that nitrogen-derived oxidants are formed in human acute lung injury and suggest that peroxynitrite may be an important oxidant in inflammatory lung disease.
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PMID:Evidence for in vivo peroxynitrite production in human acute lung injury. 769 61

The mechanisms explaining the beneficial effects of glucocorticoid in ventilator-dependent preterm infants are not known. In the present randomized trial, we evaluated the hypothesis that dexamethasone (DEX) treatment of small, preterm infants at risk for chronic lung disease favorably affects the surfactant system. Twenty-three ventilator-dependent infants, with a mean +/- SD gestational age of 26 +/- 2 wk and a mean birth weight of 836 +/- 173 g, received 1 wk of treatment with either DEX (dose 0.5 mg/kg/d) or placebo beginning at 2 wk of age. The airway specimens were analyzed for surfactant components, surface activity, surfactant inhibitors, and inflammatory mediators. The concentrations of these parameters in epithelial lining fluid were calculated using the urea method. DEX treatment decreased the concentration of nonsedimentable protein in epithelial lining fluid within 3 d (p < 0.05). The nonsedimentable fraction of airway specimens decreased the surface activity of surfactant as a function of protein concentration. At a constant protein concentration, the protein from placebo-treated infants inhibited the surface activity of human surfactant in vitro more than protein from DEX-treated infants (p < 0.05). DEX transiently increased the concentration of surfactant protein-A in epithelial lining fluid but had no effect on surface activity of the sedimentable surfactant complex or on concentrations of phosphatidylcholine, IL-1 beta, lactoferrin, or myeloperoxidase. We conclude that the acute beneficial effect of DEX treatment in preterm ventilator-dependent infants may in part be mediated through a decrease in the concentration of non-sedimentable protein and a decrease in the capacity of this protein to inhibit surface activity.
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PMID:Dexamethasone treatment of infants at risk for chronic lung disease: surfactant components and inflammatory parameters in airway specimens. 780 37

Propionibacterium acnes was identified as the pathogen in a case of subacute lung infection by examination of an open lung biopsy specimen. The patient was a 65-year-old male with exacerbation of chronic lung disease. The organism was isolated in pure culture and was present in large numbers on Gram stain. Histological examination demonstrated active interstitial fibrosis; macrophages laden with Propionibacterium acnes antigen were revealed using a peroxidase-antiperoxidase stain. This is the first report of subacute infection of pulmonary tissue due to this organism.
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PMID:Bronchopneumonia caused by Propionibacterium acnes. 784 79


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