The proteolysis theory of emphysema states that in alpha-1-antitrypsin (A1AT) deficiency, protease-antiprotease imbalances are responsible for lung destruction. This theory does not adequately explain the pathogenesis of the disease in patients with normal protease inhibitor levels in serum. Combination of autologous leukocyte lysosomal extracts containing a 12-16 fold molar excess of AAT to elastase, resulted in complete inhibition of elastolytic activity. Extended incubation, however, resulted in the appearance of elastolytic activity in a significantly increased proportion of the mixtures from COPD patients (compared to normal subjects). We have identified an activity in lysosomal extracts responsible for this activation and an activity in plasma which inhibits the activation. The work proposed for this year includes the purification, identification and characterization (electrophoretic properties, activity maxima, amino acid and carbohydrate charaterization, detection of levels, electrophoretic and functional properties in serum and leukocyte extracts) of both proteins. With the information obtained, we will attempt to correlate presence, severity or absence of disease based on lung function abnormalities, to the biochemical findings.