Role of enzymes from inflammatory cells on airway submucosal gland secretion.
We examined the roles of enzymes from mast cells and from neutrophils in stimulating airway submucosal gland secretion. To avoid effects on surface epithelial cells and goblet cells, we studied a line of cultured bovine tracheal gland serous cells. We discovered that mast cell chymase and neutrophil elastase are the most potent secretagogues of airway submucosal glands described. Mast cell chymase markedly stimulated serous cell secretion in a concentration-dependent fashion with a threshold of 10(-10) M, whereas tryptase had no effect. The response to 10(-8) M chymase (1,530 +/- 80% over baseline; mean +/- SEM) was approximately 10-fold higher than that evoked by other agonists such as histamine and isoproterenol. Both neutrophil proteases also stimulated secretion in a concentration-dependent fashion with a threshold of greater than 10(-10) M. Elastase was more potent than cathepsin G, causing a maximal secretory response of 1,810 +/- 60% over baseline at 10(-8) M. Secretion by the 3 proteases was noncytotoxic and required catalytically active enzymes. These findings suggest a potential role for neutrophil and mast cell proteases in the pathogenesis of increased and abnormal submucosal gland secretions in diseases associated with inflammation of the airways.
Nadel
J A
JA
Cardiovascular Research Institute, University of California, San Francisco.
D000818:Animals; D056649:Cathepsin G; D002403:Cathepsins / Q000502:physiology; D002417:Cattle; D002478:Cells, Cultured; D053818:Chymases; D005088:Exocrine Glands / Q000378:metabolism*; D007249:Inflammation / Q000503:physiopathology; D008407:Mast Cells / Q000201:enzymology*; D009093:Mucus / Q000378:metabolism; D009504:Neutrophils / Q000201:enzymology*; D010196:Pancreatic Elastase / Q000502:physiology; D010447:Peptide Hydrolases / Q000502:physiology; D012697:Serine Endopeptidases / Q000502:physiology; D014132:Trachea / Q000378:metabolism*
D002403:Cathepsins; D010447:Peptide Hydrolases; C023073:tosylarginine methyl ester hydrolase; D012697:Serine Endopeptidases; D056649:Cathepsin G; D010196:Pancreatic Elastase; D053818:Chymases