Proteolytic inactivation of α1-proteinase inhibitor in infected bronchial secretions from patients with cystic fibrosis

Abstract

The chronic, progressively destructive bronchitis of patients with cystic fibrosis (CF) is characterized by an important imbalance between tissue destroying granulocyte proteases such as granulocyte elastase (GE) and its physiological inhibitors in bronchial secretions. Recent in vitro studies suggest, that proteases derived from bacteria or endogenous proteases may contribute to inactivation of physiological inhibitors of GE. Since only trypsin-unreactive α1-proteinase inhibitor (α1-PI) was detected in CF bronchial secretions, we attempted to identify the mechanism of inactivation of α1-PI. We found a heat stable, serine protease-like enzymatic activity capable of degrading 125-I-labelled α1-PI extensively in 22 infected but not in one non-infected CF bronchial secretion. In infected secretions, only degraded α1-PI, which did not migrate like oxidized α1-PI in tandem-crossed immunoelectrophoresis, was detectable. We conclude, that free GE in excess as well as GE bound to bronchial mucosal inhibitor may partly account for the α1-PI-cleaving activity, but that other yet unknown bacterial or host serine proteases also contribute to α1-PI inactivation.