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Henke, M.O.* ; John, G. ; Rheineck, C.* ; Chillappagari, S.* ; Naehrlich, L.* ; Rubin, B.K.

Serine proteases degrade airway mucins in cystic fibrosis.

Infect. Immun. 79, 3438-3444 (2011)

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Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.

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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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