ELEVATED LEVELS OF MATRIX METALLOPROTEINASES IN BRONCHOALVEOLAR LAVAGE FLUID OF EMPHYSEMATOUS PATIENTS

Background - Matrix degradation in emphysema has long been attributed to the action of neutrophil elastase (NE), More recently a role for ot her proteases, particularly the matric metalloproteinases (MMPs), in t he pathogenesis of this disease has been proposed, To date, however, t he presence of MMPs ire the lungs of patients nit-h emphysema has not been demonstrated. Methods - Samples of bronchoalveolar lavage (BAL) f luid from 10 patients with emphysema and from control subjects matched for sex and current smoking status were assessed for collagenase, gel atinase, and NE activity, Pulmonary function tests and computed tomogr aphic (CT) scans were carried out on all study subjects. Results - Col lagenase activity was detected in BAL fluid samples from all emphysema tous patients bur 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 s ignificant source of the gelatinase B observed. NE was detected in six of the PD patients with emphysema and in two smoking controls (p<0.01 ), indicating that collagenase was more useful in discriminating betwe en disease and control groups than either NE or gelatinase B. No relat ionship 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 metallo proteinases ira 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.