Hypoxic Injury to Human Alveolar Macrophages Accelerates Release of Previously Bound Neutrophil Elastase

Human neutrophil elastase and other neutrophil granule constituents are internalized by human alveolar macrophages in vitro via receptor-mediated endocytosis, and immunoreactive neutrophil elastase is detectable within alveolar macrophages freshly harvested from human smokers. To gain insight into the potential role of neutrophil elastase bound by alveolar macrophages in the pathogenesis of connective tissue proteolysis, we have chosen hypoxia as a model of macrophage injury and have studied its effect upon the fate of bound neutrophil elastase. We found (1) that in a 3-h incubation after brief exposure to neutrophil elastase, control alveolar macrophages partially degraded bound enzyme, but they also released intact, enzymati-cally active, elastase in small amounts; (2) that release of TCA-insoluble radiolabeled elastase and elastase activity was enhanced fivefold and twofold over control, respectively, by alveolar macrophage injury during a 3-h incubation in humidified nitrogen; (3) that enzymatic activ...