Involvement of Leukocytic Proteases in Emphysema and Antitrypsin Deficiency

Abstract

Evidence is presented to support the postulate that leukocytic proteases may be intimately involved in pathogenesis of pulmonary emphysema associated with antitrypsin deficiency. Leukocytic proteases extracted from purulent sputum are capable of digesting human and animal lung tissues, and this enzymatic activity is strongly inhibited by the antitrypsin from normal serum. Lung tissue may have affinity for binding antitrypsin from serum and this may have some therapeutic implications. Two mechanisms are described whereby antitrypsin deficiency develops: (1) a block in the release of an abnormal antitrypsin from the liver cell and (2) increased lability of the abnormal antitrypsin molecule in the serum. Both of these mechanisms could account for the most severe deficiencies of serum antitrypsin, but increased lability alone may result in the milder deficiency states associated with some variants of the antitrypsin molecule.