The fate of neutrophil elastase incorporated by human alveolar macrophages.
Although protease-antiprotease imbalance is widely thought to contribute to the genesis of emphysema, the involvement of the alveolar macrophage in this process is poorly defined. We have quantified the uptake of radioiodinated human neutrophil elastase by human alveolar macrophages in monolayer culture and assessed the enzyme's fate during periods as long as 48 h after uptake using molecular sieve chromatography. Approximately half of the radiolabel eluted with enzymatically inactive material of molecular sizes corresponding to either degraded or alpha1-protease-inhibitor-bound elastase. The remainder of the radiolabel eluted at 29,000 daltons, in fractions containing enzyme that solubilized particulate elastin, and likely represented intact neutrophil elastase. Macrophages from smokers and nonsmokers showed similar characteristics of incorporation and disposition of neutrophil elastase. Lysates of uncultured alveolar macrophages from smokers and nonsmokers contained (mean +/- SE, n = 4) 7.4 +/- 0.8 and 3.3 +/- 1.4 ng of neutrophil elastase activity per 10(6) cells, respectively (not significant). However, as smokers have 11-fold more cells obtainable by lavage, the total lavaged elastase loads in alveolar macrophages were 561.7 +/- 72.3 and 21.3 +/- 6.8 (p less than 0.01) in smokers and nonsmokers, respectively. We conclude that the alveolar macrophage may clear and inactivate neutrophil elastase in the lung. In addition, by conserving some ingested elastase in an enzymatically active form, the macrophage may serve as an elastase reservoir. In areas of high macrophage density, as around the respiratory bronchioles of smokers, the macrophage could release a portion of the incorporated elastase and damage lung elastin.
D002470:Cell Survival; D002478:Cells, Cultured; D006801:Humans; D008264:Macrophages / Q000201:enzymology*; D009504:Neutrophils / Q000201:enzymology*; D010196:Pancreatic Elastase / Q000378:metabolism*; D011650:Pulmonary Alveoli / Q000201:enzymology*; D012907:Smoking; D007507:Therapeutic Irrigation
D010196:Pancreatic Elastase