ELASTINOLYTIC ACTIVITY OF ALVEOLAR MACROPHAGES IN SMOKING-ASSOCIATED PULMONARY-EMPHYSEMA

Current concepts of pathomechanisms leading to acquired emphysema suggest that alveolar macrophages (AM) activated by cigarette smoking may cause an elastase/antielastase imbalance localized to the microenvironment formed by phagocytes and lung tissue. A functional cell assay was used to evaluate the cell-associated elastinolytic activity of AM. AM were obtained by bronchoalveolar lavage from patients with emphysema and from patients with non obstructive chronic pulmonary diseases (non-COPD) and cultured under serum-free conditions in direct contact with H-3-labeled elastin particles. Elastinolytic activity was calculated from the released radioactivity in culture supernatants and expressed as micrograms of H-3-elastin degraded x 10(-5) AM x 72 h-1. AM of patients with emphysema had significantly higher elastinolytic activity compared to that of non-COPD patients (median: 10.8 versus 4.1 mug; P < 0.01). Further differentiation of patients revealed the lowest median activity in sarcoidosis (2.3 mug). In respect to smoking habits there was a major difference between smokers with and those without emphysema; AM of smokers with emphysema degraded more than twice the amount of elastin than smokers in the non-COPD group (median:11 versus 3.9 mug, P = 0.01). From these data we conclude that AM-derived elastinolytic proteases may be involved in the destruction of lung elastin, which is thought to be the key event occurring in the pathogenesis of pulmonary emphysema.