The role of leukocyte lysosomal elastase in the pathogenesis of obstructive lung disease

It is recognized that a potential source of proteolysis leading to pulmonary parenchymal destruction is present in polymorphonuclear leukocytes. However, measurements of leukocyte lysosomal elastase have not been reported in a large population of patients with chronic obstructive pulmonary disease (COPD) as compared with controls. Lysosomal elastase activity was measured in a leukocyte homogenate isolated from peripheral venous blood in 42 patients with COPD. 35 patients have MM Pi phenotype as did all 31 controls; 7 patients and 9 subjects with normal pulmonary function tests have abnormal Pi phenotypes. Mean age of each of the 3 groups is 57 ± 14, 43 ± 13, and 36 ± 20 yr, respectively. Elastase activity was assayed against solubilized bovine ligamentum nuchae elastin. The average of elastase activity in COPD patients with MM phenotype was 1191 mu/μg lysomal protein ± s.d. 598 as compared with 793 ± s.d. 242 in controls p<0.001. No significant differences were found between male and female subjects in either COPD or control groups. No difference was determined among individuals with abnormal phenotypes with or without COPD or controls, or those with predominant bronchitis as compared with emphysema. The variability of repeated elastase values in controls averaged 20%. These results indicate that leukocyte lysosomal elastase is significantly elevated in patients with COPD, without alpha antitrypsin deficiency, and suggest that this may be an etiologic variable in the development of parenchymal lung damage.