Interaction of Granulocyte Proteases with Inhibitors in Pulmonary Diseases

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Abstract

Sputum granulocytes were implicated as the source of proteolytic activity found in purulent bronchial secretions already by Opie.1 2 Final proof that a bulk of these proteases is of granulocytic origin was presented more recently, based on immunochemical studies utilizing specific antisera against the granulocyte proteases.3 The total concentration of these different granulocyte proteases is extremely high in purulent bronchial secretions, approaching a level of 0.5–1 g/l.3 4 In such secretions the proteases are present in a free, active form as well as in complex with the inhibitors.3 It seems reasonable to propose that these proteases are involved in the extensive tissue destructions seen in bronchiectasis, which is a rather common complication of chronic purulent bronchitis. Furthermore, pulmonary emphysema is currently thought to be due to a protease-antiprotease imbalance in the lung with uncontrolled digestion of the lung tissue, caused by granulocyte proteases — particularly elastase.5 This hypothesis is supported by the fact that persons with inherited deficiency of α1-antitrypsin, the main inhibitor of granulocyte elastase,6 show an increased susceptibility to emphysema.7 Furthermore, recent results indicate that the emphysema in cigarette smokers might be due in part to local suppression of α1-antitrypsin and also antileukoprotease in lung by oxidative agents present in cigarette smoke.8 9 In addition, granulocyte homogenates10 or purified granulocyte elastase11 cause emphysema when administered intratracheally to experimental animals. Macrophage elastase seems to be a less likely candidate to cause emphysema — at least as judged from the indirect evidence that this enzyme is poorly inhibited by α1-antitrypsin.12