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- Title
α<sub>1</sub>-Proteinase Inhibitor Abrogates Proteolytic and Secretagogue Activity of Cystic Fibrosis Sputum.
- Authors
Hansen, Gesine; Schuster, Antje; Zubrod, Chrisiiane; Wahn, Volker
- Abstract
Airway disease in cystic fibrosis (CF) is characterized by neutrophil-dominated chronic inflammation with an excess of uninhibited neutrophil elastase (NE), which is regarded as an important factor in progressive lung destruction. Therefore, inhalation of α1-proteinase inhibitor (α1-PI) seems to be a reasonable therapeutic approach. To estimate its therapeutic potential, we quantitatively investigated the in vitro interactions of exogenous α1-PI with CF sputum samples (n = 28). High NE and α1-PI concentrations were detected in CF sputum (6.03 ± 0.78 and 2.56 ± 0.16 μmol/l, respectively). There was significant NE activity (2.6 ± 0.4 U/l) due to both the surplus of NE and proteolytic degradation of α1-PI. Addition of exogenous α1-PI resulted in a dose-dependent inhibition of NE activity in CF sputum; > 90% inhibition was achieved at 10 μg/ml α1-PI. Purified NE as well as CF sputum potently induced secretion from porcine tracheal glands. Corresponding to inhibition of NE activity, CF sputum-induced secretion was also inhibited by exogenous α1-PI; > 90% inhibition was also achieved at 10 μg/ml α1-PI. Incubation of exogenous α1-PI with CF sputum for 24 h did not reduce the inhibitory effects. From our in vitro results we conclude that inhalation of α1-PI might effectively inhibit both NE activity and airway gland hypersecretion in CF airways. Copyright © 1995 S. Karger AG, Basel
- Publication
Respiration, 1995, Vol 62, Issue 3, p117
- ISSN
0025-7931
- Publication type
Article
- DOI
10.1159/000196405