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 3H-labeled elastin particles. Elastinolytic activity was calculated from the released radioactivity in culture supernatants and expressed as micrograms of 3H-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 micrograms; P < 0.01). Further differentiation of patients revealed the lowest median activity in sarcoidosis (2.3 micrograms). In respect to smoking habits there was a major difference between smokers with emphysema degraded more than twice the amount of elastin than smokers in the non-COPD group (median:11 versus 3.9 micrograms, P = 0.01). From these data we conclude that AM-derived elsatinolytic 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.
Muley
T
T
Thoraxklinik, Abteilung für Klinische Chemie, Heidelberg-Rohrbach, Germany.
Wiebel
M
M
Schulz
V
V
Ebert
W
W
D000328:Adult; D000368:Aged; D001992:Bronchoalveolar Lavage Fluid; D004549:Elastin / Q000378:metabolism*; D005260:Female; D006801:Humans; D008171:Lung Diseases / Q000201:enzymology; D016676:Macrophages, Alveolar / Q000201:enzymology*; D008297:Male; D008875:Middle Aged; D010196:Pancreatic Elastase / Q000378:metabolism*; D011656:Pulmonary Emphysema / Q000201:enzymology* / Q000209:etiology / Q000503:physiopathology; D012129:Respiratory Function Tests; D012907:Smoking / Q000009:adverse effects*
D004549:Elastin; D010196:Pancreatic Elastase