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)

Evidence is accumulating that cigarette smoking plays an important role in the protease-antiprotease imbalance in alpha 1-antitrypsin-sufficient emphysema. Since most smokers, however, do not develop emphysema, it has to be presumed that other factors in addition to smoking contribute to the origin of the imbalance. The major source of proteases is the polymorphonuclear leucocyte (PMN). We tested the hypothesis that an abnormality in the releasability of PMN might predispose for the development of emphysema. Therefore, the release of elastase, myeloperoxidase, and beta-glucuronidase from PMN was investigated in patients with emphysema and healthy controls, matched for sex, age, and smoking habits. PMN were isolated from peripheral blood and stimulated with calcium-ionophore A23187, formyl-methionyl-leucyl-phenylalanine (FMLP), and serum-treated zymosan (STZ). Total enzyme content of PMN was measured after cell lysis with Triton X-100. Total elastase, myeloperoxidase, and beta-glucuronidase content of PMN were not significantly different in healthy subjects and patients with emphysema. In vitro release of elastase and myeloperoxidase from both stimulated and unstimulated PMN was not significantly different in healthy subjects and emphysematous patients. Moreover, no differences were found between smoking and ex-smoking individuals. Beta-glucuronidase release tended to be lower in patients with emphysema than in healthy controls. We conclude that an abnormality in the releasability of peripheral PMN is unlikely to be a pathogenetic factor in emphysema.
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PMID:In vitro release of neutrophil elastase, myeloperoxidase and beta-glucuronidase in patients with emphysema and healthy subjects. 166 65

LSP contents of sputum samples from patients with chronic airway diseases were measured by an enzyme-linked immunosorbent assay (ELISA) kit which was designed by Kuroki et al to examine whether a substance identical to lung surfactant contained in alveolar lining layer, is also contained in respiratory tract fluid or not in the ELISA kit. One antibody to LSP was conjugated to peroxidase and another one to LSP was fixed onto a bead. A neo-anionic detergent, Triton X-100 and an anionic detergent, sodium dodecyl sulfate (SDS) were added to extraction medium to separate LSP from lung surfactant, and LSP reaction of sputum sample was maximal when the ratio of Triton X-100 to SDS was in range of 1 to 4. Airway mucous glycoprotein (AMG) purified from sputum sample did not show any LSP reaction. In CsCl density gradient ultracentrifugation of whole sputum, the LSP reaction was detectable only in the top fraction with density of about 1.40 and AMG was located in the fraction with a density of about 1.50. These results indicate that the LSP reaction of sputum sample is not due to false reaction caused by nonspecific binding of viscous AMG to the two antibodies to LSP, but to the existence of LSP. Therefore it was concluded that lung surfactant is contained in respiratory tract fluid. In general, the LSP concentrations in sputum samples were lower in purulent sputa than in mucoid or mucopurulent sputa, and lower in patients with diffuse panbronchiolitis and bronchiectasia than in those with pulmonary emphysema and chronic bronchitis. It was shown that LSP was hydrolyzed by neutrophil leucocyte homogenate. These results suggest that LSP content of sputum is influenced by various factors such as infection and disease in the respiratory tract, and thus is useful to estimate pathological states of chronic airway diseases.
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PMID:[Lung surfactant apoprotein (LSP) content of sputum samples from patients with chronic airway diseases]. 221 2

The purpose of this study was to assess the effects of elastase-induced pulmonary emphysema and the inhalation of an irritant aerosol (Triton X-100, a nonionic surfactant similar to those used in a number of pressurized consumer products) on pulmonary deposition and retention of an insoluble test aerosol, 59Fe-labeled Fe2O3. Untreated rats or rats pretreated by intratracheal instillation with elastase were exposed to an aerosol of 59Fe-labeled Fe2O3 either 18 hr or 7 days after exposure to aerosolized Triton X-100 which was administered in doses of 20, 100, or 200 micrograms/g of lung. Rats pretreated with elastase had significantly lower pulmonary deposition of 59Fe than the untreated controls (p less than 0.005). Pulmonary deposition of Fe2O3 was unaffected by pretreatment with Triton X-100. Elastase treatment alone had no effect on retention of Fe2O3. Triton X-100 administered 18 hr prior to exposure of rats to Fe2O3 aerosol resulted in dose-related increases in whole-body retention of 59Fe. When rats were exposed to Triton X-100 7 days before exposure to Fe2O3, increased retention of 59Fe was noted only in those treated at the highest Triton X-100 dose level (200 micrograms/g).
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PMID:Influence of elastase-induced emphysema and the inhalation of an irritant aerosol on deposition and retention of an inhaled insoluble aerosol in Fischer-344 rats. 655 16

Excessive proteolytic activity of proteinase 3 (Pr3) has been suggested to be a factor contributing to the pathogenesis of emphysema and other inflammatory disorders. We report here on the kinetics of inhibition of Pr3 by one of its major endogenous inhibitors, the 6-kD inhibitory domain of elafin. The results are consistent with a reaction mechanism in which a single elafin molecule binds a single Pr3 molecule to form a fully reversible complex. The association and dissociation rate constants, and the inhibition constant were measured to be 4.0 x 10(6) M(-1) s(-1), 1.7 x 10(-3) s(-1), and 4.2 x 10(-10) M, respectively. Triton X-100 and dimethyl sulfoxide, which are frequently added in assay mixtures for enzymatic analysis of Pr3 activity, significantly reduced the association rate. A fraction of the total neutrophil content of Pr3 has been reported to be bound to the surface of the plasma membrane of activated and nonactivated neutrophils. In this study, we also measured the reaction rate constants of elafin with Pr3 that had been previously allowed to associate with phospholipid bilayer vesicles. Binding to the model membranes slowed down the association rate to 3.3 x 10(5) M(-1) s(-1), but the membrane-bound Pr3 and elafin formed a more stable complex, with a dissociation rate constant of 9.1 x 10(-4) s(-1). Based on the kinetic parameters determined here and the estimated elafin concentrations in vivo, it may be concluded that elafin plays a limited role in the regulation of proteolytic activity of Pr3 in lung secretions.
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PMID:Kinetics of the inhibition of proteinase 3 by elafin. 1115 54