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Serine proteases degrade airway mucins in cystic fibrosis.
Infect. Immun. 79, 3438-3444 (2011)
Airway mucins are the major molecular constituents of mucus. Mucus forms the first barrier to invading organisms in the airways and is an important defense mechanism of the lung. We confirm that mucin concentrations are significantly decreased in airway secretions of subjects with cystic fibrosis (CF) who have chronic Pseudomonas aeruginosa (PA) infection. In sputum from CF subjects without a history of PA, we found no significant difference in the mucin concentration compared to mucus from normal controls. We demonstrate that mucins can be degraded by synthetic human neutrophil elastase (HNE) and PA-elastase-B (pseudolysin) and that degradation was inhibited by the serine proteases inhibitors (diisopropyl fluorophosphates (DFP), phenylmethyl sulfonyl fluoride (PMSF), and 1-chloro-3-tosylamido-7-amino-2-heptanone HCl (TLCK)). The mucin concentration in airway secretions from CF subjects is similar to normal subjects until there is infection by PA, and after that, the mucin concentration decreases dramatically. This is most likely due to degradation by serine proteases. The loss of this mucin barrier may contribute to chronic airway infection in the CF airway.
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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
no keywords
Language
english
Publication Year
2011
HGF-reported in Year
2011
ISSN (print) / ISBN
0019-9567
e-ISSN
1098-5522
Journal
Infection and Immunity
Quellenangaben
Volume: 79,
Issue: 8,
Pages: 3438-3444
Publisher
American Society for Microbiology (ASM)
Reviewing status
Peer reviewed
Institute(s)
Institute of Lung Health and Immunity (LHI)
POF-Topic(s)
30202 - Environmental Health
Research field(s)
Lung Research
PSP Element(s)
G-505000-007
PubMed ID
21646446
WOS ID
WOS:000292770300048
Scopus ID
79961121946
Erfassungsdatum
2011-07-01