Elevated levels of matrix metalloproteinases in bronchoalveolar lavage fluid of emphysematous patients

摘要

BACKGROUND: Matrix degradation in emphysema has long been attributed to the action of neutrophil elastase (NE). More recently a role for other proteases, particularly the matrix metalloproteinases (MMPs), in the pathogenesis of this disease has been proposed. To date, however, the presence of MMPs in the lungs of patients with emphysema has not been demonstrated. METHODS: Samples of bronchoalveolar lavage (BAL) fluid from 10 patients with emphysema and from control subjects matched for sex and current smoking status were assessed for collagenase, gelatinase, and NE activity. Pulmonary function tests and computed tomographic (CT) scans were carried out on all study subjects. RESULTS: Collagenase activity was detected in BAL fluid samples from all emphysematous patients but in only one smoking control (p < 0.001). Gelatinase B was present in six patients and in two smoking controls (p < 0.03). The concomitant presence of gelatinase B in complex with lipocalin (NGAL) in the gelatinase positive samples suggests that the neutrophil is a significant source of the gelatinase B observed. NE was detected in six of the 10 patients with emphysema and in two smoking controls (p < 0.01), indicating that collagenase was more useful in discriminating between disease and control groups than either NE or gelatinase B. No relationship was observed between any of the enzymes measured and pulmonary function or CT density score. CONCLUSIONS: This study demonstrates, for the first time, the presence of increased levels of matrix metalloproteinases in the lungs of patients with emphysema and suggests that, in BAL fluid, collagenase activity may be a better indicator of the presence of emphysema than elastase.