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Altered Protease And Antiprotease Balance During A Copd Exacerbation Contributes To Mucus Obstruction, Shashi Chillappagari, Jenni Preuss, Sebastian Licht, Christian Müller, Poornima Mahavadi, Gaurav Sarode, Claus Vogelmeier, Andreas Guenther, Lutz Narlich, Bruce K. Rubin, Markus O. Henke

Pediatrics Publications

Background

Proteases have been shown to degrade airway mucin proteins and to damage the epithelium impairing mucociliary clearance. There are increased proteases in the COPD airway but changes in protease-antiprotease balance and mucin degradation have not been investigated during the course of a COPD exacerbation. We hypothesized that increased protease levels would lead to mucin degradation in acute COPD exacerbations.

Methods

We measured neutrophil elastase (NE) and alpha 1 protease inhibitor (A1-PI) levels using immunoblotting, and conducted protease inhibitor studies, zymograms, elastin substrate assays and cigarette smoke condensate experiments to evaluate the stability of the gel-forming mucins, MUC5AC and MUC5B, …