Fate of human neutrophil elastase following receptor-mediated endocytosis by human alveolar macrophages. Implications for connective tissue injury.
AM may be important in the pathogenesis of centrilobular emphysema of cigarette smokers because smokers' AM release elastolytic activity into culture medium and an expanded population of AM is found in lung regions of smokers where destructive lesions occur. AM are capable of receptor-mediated endocytosis of neutrophil elastase in vitro, but little has been known about the fate of the enzyme after endocytosis. We have observed that after brief exposure to HLE in vitro, (1) CEs of cultured human AM contain detectable quantities of neutrophil elastase and elastase activity for days; (2) endocytosed neutrophil elastase is slowly degraded by the macrophages; (3) neutrophil elastase and elastase activity are slowly released into the culture medium conditioned by the macrophages; (4) elastase activity released into CM by the macrophages has catalytic properties of neutrophil elastase; and (5) elastase released into CM during 5 days in culture is fourfold greater than the initial elastase activity of the CEs, suggesting that enzymatic activity of endocytosed elastase is masked by an intracellular inhibitor. Thus macrophages both degrade and release endocytosed neutrophil elastase and may play a very complex role in modulation of neutrophil elastase injury to connective tissue in the lung and other tissues.
D002478:Cells, Cultured; D003470:Culture Media; D004705:Endocytosis; D006801:Humans; D007700:Kinetics; D008264:Macrophages / Q000502:physiology*; D009504:Neutrophils / Q000201:enzymology*; D010196:Pancreatic Elastase / Q000378:metabolism*; D011650:Pulmonary Alveoli / Q000166:cytology*; D012907:Smoking
D003470:Culture Media; D010196:Pancreatic Elastase