Mucus hypersecretion in bronchiectasis. The role of neutrophil proteases.
To investigate the role of neutrophil proteases in the pathogenesis of mucus hypersecretion in bronchiectasis, we collected sputum samples from seven patients with bronchiectasis and measured their secretagogue activity by examining secretion of radiolabeled macromolecules by bovine airway submucosal gland cells incubated with sputum supernatants. There was marked secretagogue activity in bronchiectasis sputum, reaching a maximum of 1,963 +/- 292% (mean +/- SEM) above baseline at 1:15 dilution. Addition of ICI 200,355 (10(-5) M), a selective human neutrophil elastase inhibitor, decreased the secretory response markedly (72.53 +/- 5.89% reduction). The combination of aprotinin, an inhibitor of cathepsin G, and ICI 200,355 caused significantly more reduction in the secretory response than ICI 200,355 alone (89.12 +/- 3.8 versus 72.53 +/- 5.89% reduction, p < 0.05). We conclude that bronchiectasis sputum causes a large secretory response from tracheal submucosal glands due mostly to neutrophil proteases.
D000328:Adult; D000368:Aged; D000818:Animals; D007611:Aprotinin / Q000494:pharmacology; D001987:Bronchiectasis / Q000201:enzymology / Q000503:physiopathology*; D056649:Cathepsin G; D002403:Cathepsins / Q000037:antagonists & inhibitors / Q000502:physiology*; D002417:Cattle; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D019272:Leukocyte Elastase; D046911:Macromolecular Substances; D008297:Male; D008875:Middle Aged; D009093:Mucus / Q000378:metabolism*; D009842:Oligopeptides / Q000494:pharmacology; D010196:Pancreatic Elastase / Q000037:antagonists & inhibitors / Q000502:physiology*; D012697:Serine Endopeptidases; D013183:Sputum / Q000201:enzymology / Q000502:physiology; D014132:Trachea / Q000378:metabolism
D046911:Macromolecular Substances; D009842:Oligopeptides; C069366:ICI 200355; D007611:Aprotinin; D002403:Cathepsins; D012697:Serine Endopeptidases; C534094:CTSG protein, human; D056649:Cathepsin G; D010196:Pancreatic Elastase; D019272:Leukocyte Elastase