Taylor, Joseph C.

Abstract The granulocyte lysosomal elastase of 17 patients with chronic obstructive pulmonary disease and of 27 normal subjects was examined. Serum a 1-antitrypsin phenotypes were identical in the 2 groups: 88 per cent were type PiM and 12 per cent were type PiMS. Electrophoresis of granulocyte lysosomal extracts at pH 8.6 revealed interindividual differences in the electrophoretic mobility of the elastase enzyme. The elastases clustered into 3 regions of electrophoretic mobility, which we designated as fast (>29 mm), intermediate (24 through 29 mm), and slow (<24 mm) migration. A comparison of the number of patients and normal subjects in each electrophoretic category showed an almost 4-fold increase in the prevalence of the slow electrophoretic type of elastase in the patient group compared to the normal subjects. Esterase activity in lysosomal extracts against the synthetic elastase substrate N-t-BOC-L-alanine-p-nitrophenyl ester (NBA) varied within a 4 to 5-fold range in both patient and normal populations. No significant differences in the mean esterase activities between the patient group and the normal group could be detected within each elastase category (slow, intermediate, or fast mobility). The mean elastase NBA esterase activity was lowest in the slow elastase electrophoretic category and highest in the fast elastase type. Mean esterase activity in the intermediate electrophoretic category was intermediate between those of the slow and the fast electrophoretic types of elastase. The increase in the number of patients in the slow electrophoretic category with lowest mean elastase esterase activity suggests that qualitative rather than quantitative aspects of elastase may be critical in the pathogenesis of chronic obstructive pulmonary disease in patients with normal a 1-antitrypsin phenotypes.