Elastase inhibitors of the respiratory tract

Lung secretions contain several elastase inhibitors although alpha 1-antitrypsin (alpha 1AT) and antileukoprotease (ALP) are the major ones. Studies of lung alpha 1AT show that the inhibitor is usually partly inactive. In patients with established lung disease this is due to a combination of proteolytic degradation, complex with enzyme and oxidation at the active site. Studies in subjects with normal lungs demonstrate that the alpha 1AT is also partly inactivated although not by any of the recognised mechanisms. Furthermore no difference in function is found between current smokers and nonsmokers. ALP is largely an inhibitor of the major airways although it is still present in the lower airway secretions collected by lavage in healthy subjects. The proportions of alpha 1AT to ALP vary in patients with alpha 1AT deficiency (1:9), established emphysema (1:1) and subjects with healthy lungs (10:1). These differences affect the ability of the lavage fluids to inhibit neutrophil elastase during prolonged incubation with enzyme substrate. The results suggest that the relative concentrations of alpha 1AT and ALP, particularly in close proximity to lung substrates, may determine the degree of connective tissue destruction.