A comparison of the binding and fate of internalized neutrophil elastase in human monocytes and alveolar macrophages.
Human alveolar macrophages (AM) bind and internalize neutrophil elastase (NE) in vitro by receptor-mediated endocytosis. Blood monocytes are progenitors of AM, and if they possess receptors for NE, they could bind and internalize NE in the pulmonary interstitium and may effect elastin degradation, which likely accompanies the development of emphysema. To determine whether monocytes contain receptors for NE, radioiodinated NE (I-NE) binding was assessed, and the results were compared with binding of I-NE to AM obtained concurrently from the same donors. The binding of I-NE to monocytes cultured in vitro for 8 days was also assessed. Specific binding of I-NE to monocytes and AM reached 80% of maximum in 30 min; similar quantities bound to AM and monocytes after a 2-h incubation with I-NE, and a smaller quantity bound to cultured monocytes. The estimated association constant for specific binding was 6 X 10(6)M-1 and 4 X 10(6)M-1 for AM and monocytes, respectively. The fate of I-NE in monocytes and AM at 24 h after uptake was assessed and compared using molecular sieve chromatography. Approximately 50% of the I-NE initially bound to either monocytes or AM remained cell-associated at the end of culture; 62 to 65% of this material eluted at 29,000 daltons and solubilized particulate elastin.(ABSTRACT TRUNCATED AT 250 WORDS)
D000293:Adolescent; D000328:Adult; D001665:Binding Sites; D002478:Cells, Cultured; D003470:Culture Media; D004549:Elastin / Q000378:metabolism*; D004705:Endocytosis; D006801:Humans; D008264:Macrophages / Q000201:enzymology*; D009000:Monocytes / Q000201:enzymology*; D009504:Neutrophils / Q000201:enzymology*; D010196:Pancreatic Elastase / Q000378:metabolism*; D011650:Pulmonary Alveoli / Q000201:enzymology* / Q000378:metabolism; D011656:Pulmonary Emphysema / Q000209:etiology; D011956:Receptors, Cell Surface / Q000032:analysis
D003470:Culture Media; D011956:Receptors, Cell Surface; D004549:Elastin; D010196:Pancreatic Elastase