Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0034067 (emphysema)
 11,506 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Experimental emphysema in the guinea pig was made by intracheal instillation of porcine pancreatic elastase in order to analyze the proteolytic factors related to the pathogenesis of pulmonary emphysema. Ultrastructural and morphometric studies were performed in the elastase-induced emphysema in vivo. The following results were obtained: 1) Ultrastructural studies in vivo revealed that interstitial edema and degradation of fibrous tissue already occurred 2 hours after elastase instillation. Subsequently we observed fragmentations of elastin and dissociation between elastic tissue and collagen fibers 2 days later. Apparent degradation and fragmentation of elastin was found after 7 days. 2) Morphometric studies by electron microscope on elastase-induced experimental emphysema showed significant degradation of elastin fragments. Thus, it was suggested the importance of elastolytic process on the pathogenesis of pulmonary emphysema.
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PMID:Ultrastructural studies of elastase-induced experimental emphysema. 50 80

Intravenous administration of porcine pancreatic elastase to hamsters produced significant loss of elastic recoil at low volumes. Histology and mean linear intercept of the lungs fixed at a pressure of 20 cm H2O and studied for 3 weeks after administration of elastase were normal. Larger doses of elastase caused immediate fatal, hemorrhagic pulmonary edema. These results confirmed previous morphologic observations of the effects of intravenously administered elastase, but demonstrated that the loss of elastic recoil at low lung volumes is not invariably associated with histologic changes or morphologically with loss of elastin fibers. These observations suggest that submicroscopic lesions may be present and may antedate the earliest morphologic evidence of emphysema and aging in the lung.
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PMID:Physiologic and morphologic observations of the effects of intravenous elastase on the lung. 61 30

The intratracheal injection of pancreatic elastase results in an acute loss of elastin from the lungs of hamsters and the development of emphysema. We used measurements of the unique covalent cross linking amino acids of elastin, desmosine and isodesmosine, to quantitate elastin. Direct measurements on the lungs estimated an average loss of elastin of 57% after elastase injection. Elastin breakdown products were also quantitated in the urine and feces after injection. An average of 8.8 nmol of desmosines was recovered from the urine of each hamster. This amount represented the desmosines from 61% of the elastin lost from the lungs. Desmosine and isodesmosine existed in the urine in peptide fractions that ranged from 9 to 27,000 daltons with an average of 13,000. Only trace quantities of desmosines could be detected in feces. Desmosines injected intraperitoneally were completely recovered in the urine, and radioactive tracer studies failed to reveal in vivo catabolism of injected desmosines. These results suggest that measurement of urinary desmosines holds promise for the study of elastin turnover.
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PMID:Urinary excretion of elastin peptides containing desmosin after intratracheal injection of elastase in hamsters. 65 92

Human neutrophilic polymorphonuclear leukocyte (PMN) elastase was purified by affinity chromatography to greater than 95% homogeneity as judged by disc-gel electrophoresis. Dog lung elastin was prepared from alveolar-enriched tissue by prior extraction of soluble and collagenous lung proteins with 0.1 M NaOH at 98 degrees C. Digestion of the remaining insoluble residue by the purified PMN enzyme was monitored by Lowry assay of acid-soluble peptides released. The PMN enzyme possessed 60% of the digestive activity of crystallized porcine pancreatic elastase (weight:weight comparison) when tested in vitro against this substrate in phosphate-NaCl buffer at pH 7.5. Whole tissue studies were then performed in lungs of laboratory animals. One-ml samples containing purified PMN elastase were instilled into lavaged and saline-perfused isolated dog lung at the level of the sixth to seventh generation bronchus. Treatment with 384 mug of the PMN enzyme produced anatomic emphysema after a 90-min incubation at room temperature, which was comparable to that produced by 100 mug of porcine pancreatic elastase. Frozen sections of treated and control lungs were examined for the presence of PMN elastase by the indirect immunoperoxidase method using a monospecific rabbit antiserum against PMN elastase as the primary stain. Light microscopy revealed elastase bound to connective tissue in the treated lungs, in close proximity to aldehyde-fuchsin-counterstained elastic fibers. A similar experiment was tn of enzyme solutions containing 1;0 mg of elastase per ml produced discrete lesions within 90 min, as before. Light microscopic studies in conjunction with the indirect immunoperoxidase staining method again demonstrated elastase in association with connective tissue elements in the lesion area. In addition, part of the instilled protease could be demonstrated within alveolar macrophages. Electron microscopy combined with immunoperoxidase staining revealed direct attachment of th einstilled enzyme to elastic fibers within alveolar septa. In enzyme-treated tissue, some septa showed severe depletion of intercellular structures with the exception of colalgen, which was generally preserved. These results show that human leukocyte elastase penetrated dog alveolar septal connective tissue after airway instillation and that the enzyme attaches to elastic fibers, inducing histologic changes comparable to thos seen in human emphysema.
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PMID:Experimental emphysema induced with purified human neutrophil elastase: tissue localization of the instilled protease. 84 56

Purified human leukocyte elastase was injected into the tracheas of 46 hamsters. Thirteen animals died spontaneously within 1 week, with extensive lung hemorrhage. The elastin content of the lungs was only slightly less than control values 3 hours after injection. At 2 months, the lungs of the remaining animals showed mild, patchy emphysema and morphometric changes consistent with emphysema. These results contrasted with the effects of a similar elastolytic dose of pancreatic elastase administered to 26 other hamsters in that only one animal died spontaneously, the lung elastin content 3 hours after injection was substantially decreased, and severe emphysema was present 2 months later. Leukocyte elastase appears to be capable of causing emphysema; but unlike pancreatic elastase, leukocyte elastase produces emphysema that is mild, even at a dose sufficient to produce intense lung hemorrhage and a high mortality.
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PMID:The induction of pulmonary emphysema with human leukocyte elastase. 90 Jun 34

Alveolar macrophages from smokers, in contrast to those of non-smokers, release elastase into serum-free culture medium. Since enzymes that digest elastin produce pulmonary emphysema in experimental animals, release of elastase by alveolar macrophages from smokers suggests that these cells are important in the pathogenesis of emphysema of smokers.
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PMID:Elastase release from human alveolar macrophages: comparison between smokers and nonsmokers. 91 Jan 31

During pathologies such as arteriosclerosis and emphysema, degradation of elastin by elastases occurs and elastin peptides are produced. In order to evaluate elastin degradation, measurements of elastin peptide concentration in human blood were carried out. According to elastin peptides used for obtention of antibodies and for ELISA, the measured values are different. Elastin peptides have several biological effects: they are chemotactic, modify ion fluxes and several intracellular mechanisms.
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PMID:[Elastin and arteriosclerosis: determination and characterization of elastin peptides in blood]. 130 Dec 21

Proteinase-3 (PR-3) is a neutral serine proteinase present in the azurophil granules of human polymorphonuclear leukocytes. It degrades a variety of extracellular matrix proteins including elastin in vitro and causes emphysema when administered by tracheal insufflation to hamsters. It is identical to the target autoantigen (c-ANCA) associated with Wegener's granulomatosis and to myeloblastin, a serine proteinase first identified in HL-60 leukemia cells. In this study, the gene encoding PR-3 was cloned and sequenced. The gene spans approximately 6.5 kilobase pairs and consists of five exons and four introns. The genomic organization of PR-3 is similar to that of the other serine proteinases expressed in hemopoietic cells. Each residue of the catalytic triad of PR-3 is located on a separate exon, and the positions of the residues within the exons are similar to those in human leukocyte elastase and cathepsin G. The phase and placement of the introns in the PR-3 gene are also similar to those in human leukocyte elastase and cathepsin G. The 400-base pair (bp) 5'-flanking sequence of the PR-3 gene contains a TATA box at position 379. There is no CAAT box promoter element. The 3'-untranslated region is 200 bp, extending from a TGA stop codon to the site of polyadenylation 10 bp after the canonical AATAAA signal. Amplification of PR-3 from a human/hamster hybrid cell line localizes the gene to human chromosome 19. Evidence from Northern analysis suggests that PR-3 expression is primarily confined to the promyelocytic/myelocytic stage of bone marrow development.
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PMID:Structure, chromosomal assignment, and expression of the gene for proteinase-3. The Wegener's granulomatosis autoantigen. 140 Apr 30

Pulmonary emphysema is likely to be the result of elastic tissue digestion by unrestrained elastase activity in the lung. Elastin breakdown by elastases results in the release of soluble elastin fragments (EDP), which may be measured in plasma by an ELISA. Plasma EDP levels measured using an ELISA were determined in the following groups: disease-free children (n = 24), 0.162 +/- 0.082 ng/ml; disease-free adult nonsmokers (n = 114), 1.74 +/- 0.8 ng/ml; smokers (n = 68), 2.76 +/- 4.59 ng/ml; reformed smokers (n = 43), 1.91 +/- 1.14 ng/ml. Adults with established pulmonary emphysema (n = 50), as defined by bullous formation on the chest radiograph, had levels of 50.83 +/- 24.8 ng/ml, significantly higher than the disease-free groups at p < 0.01. Pulmonary emphysema can be reflected by pulmonary function tests, especially those that measure the pulmonary elastic properties, and by computed tomographic (CT) scan percent emphysema score. We therefore examined the relationship of plasma EDP to these other indicators of pulmonary emphysema in a separate group of 26 subjects using elastic recoil measurements (K), and a further group of 30 subjects with CT scan percent emphysema score. A significant correlation of p < 0.001 was shown for plasma EDP and K and a significant correlation of p < 0.01 was shown for plasma EDP and CT scan percent emphysema score, these correlations suggesting that plasma EDP levels are indicators of the loss of pulmonary distensibility and of mild to moderate pulmonary emphysema. These findings suggest that pulmonary emphysema is characterized by active elastin breakdown.
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PMID:Plasma elastin-derived peptide levels in normal adults, children, and emphysematous subjects. Physiologic and computed tomographic scan correlates. 144 63

Current theories of pathogenesis suggest that pulmonary emphysema develops in humans because of progressive loss or derangement of lung elastin through a process mediated by elastolytic enzymes released by inflammatory cells. Neutrophils are considered primary etiologic factors because these cells produce and release two potent serine proteinases that cause emphysema when instilled into the lungs of animals. It has been suggested that alveolar macrophages also contribute to the development of emphysema through production of several enzymes with elastolytic activity, including the lysosomal cysteine proteinases cathepsin B and cathepsin L, but this has not been verified experimentally. In the current study, we instilled 115 micrograms of active cathepsin B into the lungs of hamsters three times at 48-h intervals. After 6 wk microscopic evaluation revealed that lung sections of five of seven animals given cathepsin B contained focal areas of enlarged and distorted alveoli, in the absence of fibrosis, which were similar to changes seen in the lungs of animals given papain intratracheally. Morphometrically, mean linear intercept (micron) values were significantly higher (p less than 0.025) in animals given cathepsin B (204.4 +/- 20.8) as compared with control animals (173.2 +/- 7.8), and internal surface area (sqcm) values were significantly lower (935 +/- 120 versus 1,083 +/- 56 in control animals), thereby confirming that airspace enlargement had developed after instillation of the enzyme. Lung volumes (ml) and compliance (ml/cm H2O) were not significantly higher in animals given cathepsin B.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Induction of emphysema in hamsters by intratracheal instillation of cathepsin B. 154 48


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