Immunolocalization of elastase in human emphysematous lungs.
The current working hypothesis concerning the pathogenesis of human pulmonary emphysema proposes that neutrophils migrate through the alveolar interstitium and degranulate, releasing proteolytic enzymes into the interstitium. These enzymes, in particular elastase, can bind to and degrade interstitial elastin. This report describes an immunohistochemical, ultrastructural technique that utilizes polyclonal antibodies to localize neutrophil elastase in human lungs. Using both the immunoperoxidase and the immunogold methods on thin, embedded sections of surgically resected human emphysematous lung tissue, elastase was localized in neutrophils in the lung interstitium and extracellularly in association with interstitial elastic fibers in human lungs that showed local emphysema of varying severity. Quantitative morphometric data were obtained from the lungs of eight patients undergoing lobectomy for removal of pulmonary carcinomas. Patients had preoperative forced expiratory volume (FEV1)% levels ranging from 55 to 77. There was a correlation between a quantitative measure of the local distribution of neutrophil elastase in contact with alveolar interstitial elastin and the local presence of emphysematous change as determined by mean linear intercept of the various histologic sections. These data support the validity of the "protease-protease inhibitor balance hypothesis" as an explanation of the pathogenesis of human pulmonary emphysema.
D000328:Adult; D000368:Aged; D002283:Carcinoma, Bronchogenic / Q000201:enzymology; D004549:Elastin / Q000032:analysis; D005110:Extracellular Space / Q000201:enzymology / Q000648:ultrastructure; D005260:Female; D006046:Gold; D006801:Humans; D007124:Immunoenzyme Techniques; D008168:Lung / Q000201:enzymology* / Q000648:ultrastructure; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000201:enzymology / Q000648:ultrastructure; D010196:Pancreatic Elastase / Q000032:analysis*; D011233:Precipitin Tests; D011650:Pulmonary Alveoli / Q000201:enzymology / Q000648:ultrastructure; D011656:Pulmonary Emphysema / Q000201:enzymology* / Q000473:pathology
D006046:Gold; D004549:Elastin; D010196:Pancreatic Elastase