BACKGROUND: Proteases have been shown to degrade airway @entity3558 proteins and to damage the epithelium impairing mucociliary clearance. There are increased proteases in the @entity1030 airway but changes in protease-antiprotease balance and @entity3558 degradation have not been investigated during the course of a @entity1030 . We hypothesized that increased protease levels would lead to @entity3558 degradation in acute @entity1030 exacerbations. METHODS: We measured neutrophil elastase (NE) and @entity6417 ( @entity6417 ) levels using immunoblotting, and conducted protease inhibitor studies, zymograms, @entity2362 substrate assays and cigarette smoke condensate experiments to evaluate the stability of the gel-forming mucins, @entity5089 and @entity5090 , before and 5-6  weeks after an acute pulmonary exacerbation of @entity1030 (n   =   9 subjects). RESULTS: Unexpectedly, @entity3558 concentration and @entity3558 stability were highest at the start of the exacerbation and restored to baseline after 6  weeks. Consistent with these data, immunoblots and zymograms confirmed decreased NE concentration and activity and increased @entity6417 at the start of the exacerbation. After recovery there was an increase in NE activity and a decrease in @entity6417 levels. In vitro, protease inhibitor studies demonstrated that @entity563 proteases played a key role in @entity3558 degradation. @entity3558 stability was further enhanced upon treating with cigarette smoke condensate (CSC). CONCLUSION: There appears to be rapid consumption of secreted proteases due to an increase in antiproteases, at the start of a @entity1030 . This leads to increased @entity3558 gel stability which may be important in trapping and clearing infectious and inflammatory mediators, but this may also contribute acutely to @entity6112 .

Altered protease and antiprotease balance during a XXXX contributes to mucus obstruction.

@entity6417 :: ('5265', 'Gene') :: ['A1-PI', 'alpha 1 protease inhibitor'] @entity6112 :: ('MESH:D016055', 'Disease') :: ['mucus retention'] @entity2362 :: ('2006', 'Gene') :: ['elastin'] @entity563 :: ('CHEBI:17822', 'Chemical') :: ['serine'] @entity5090 :: ('727897', 'Gene') :: ['MUC5B'] @entity5089 :: ('4586', 'Gene') :: ['MUC5AC'] @entity3558 :: ('100508689', 'Gene') :: ['Mucin', 'mucin'] @entity1030 :: ('MESH:D029424', 'Disease') :: ['COPD', 'COPD exacerbation']
@entity1030 :: (MESH:D029424,Disease) :: ['COPD exacerbation']
