Inactivation of Bronchial Mucous Proteinase Inhibitor by Cigarette Smoke and Phagocyte-Derived Oxidants

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Abstract
Freshly prepared aqueous solutions of cigarette smoke suppressed the elastase inhibitory capacity (EIC) of the acid-stable proteinase inhibitor present in bronchial mucus (BMPi) and human seminal plasma (HUSI-I). Thin-layer gel-immuno filtration analysis of mixtures of smoke-treated BMPi and human leukocyte elastase showed decreased elastase: BMPi complexes, increased uncomplexed BMPi and increased free elastase. Phenolic antioxidants prevented the suppression of the EIC of BMPi or HUSI-I by cigarette smoke. In addition, treatment of BMPi or HUSI-I with chemical oxidants caused a similar suppression of EIC. Furthermore, treatment of BMPi or HUSI-I with the phagocyte-derived oxidizing system, myeloperoxidase + H2O2 + Cl−, suppressed EIC. Finally, the functional activity of BMPi was significantly reduced in tracheal aspirates of human smokers compared to that of nonsmokers. These results support the hypothesis that local inactivation of BMPi in the conducting airways of the lung by inhaled cigarette smoke or by phagocyte-derived oxidants may play a role in the pathogenesis of obstructive lung disease in smokers.