title: Serine proteases degrade airway mucins in cystic fibrosis.
abstract: 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 infection. In sputum from CF subjects without a history of P. aeruginosa, 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 P. aeruginosa elastase B (pseudolysin) and that degradation was inhibited by serine proteases inhibitors (diisopropyl fluorophosphates [DFP], phenylmethylsulfonyl 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 that for normal subjects until there is infection by P. aeruginosa, 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.
authors.affiliation: Department of Pulmonary Medicine, Philipps-University Marburg, Baldingerstraße 1, 35043 Marburg, Germany. markus.henke@staff.uni-marburg.de
authors.forename: Markus O
authors.initials: MO
authors.lastname: Henke
authors.forename: Gerrit
authors.initials: G
authors.lastname: John
authors.forename: Christina
authors.initials: C
authors.lastname: Rheineck
authors.forename: Shashi
authors.initials: S
authors.lastname: Chillappagari
authors.forename: Lutz
authors.initials: L
authors.lastname: Naehrlich
authors.forename: Bruce K
authors.initials: BK
authors.lastname: Rubin
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D002675:Child, Preschool; D002908:Chronic Disease; D003550:Cystic Fibrosis / Q000503:physiopathology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009077:Mucins / Q000378:metabolism*; D009504:Neutrophils / Q000201:enzymology; D010196:Pancreatic Elastase / Q000378:metabolism*; D011552:Pseudomonas Infections / Q000473:pathology / Q000503:physiopathology*; D011550:Pseudomonas aeruginosa / Q000201:enzymology* / Q000302:isolation & purification; D012137:Respiratory System / Q000503:physiopathology*; D057057:Serine Proteases / Q000378:metabolism*; D055815:Young Adult
chemical_list: D009077:Mucins; D057057:Serine Proteases; D010196:Pancreatic Elastase