The effect of neutrophil protenase enzymes on the release of mucus from feline and human airway cultures.
Neutrophils may be central in the pathogenesis of several airway diseases. The effect of two neutrophil products upon mucus release from feline and human airways was examined in vitro. Neutrophil elastase (HNE) and cathepsin G (HCG) were equipotent in stimulating mucus release from feline trachea. A potential mechanism of the mucus release was studied by exposure to HNE and various inhibitors of serine proteases or eicosanoid metabolism. Coincubation with the serine protease inhibitor, chloromethylketone, completely blocked HNE-stimulated mucus release. The putative selective cyclooxygenase inhibitor, ibuprofen, did not alter HNE-stimulated mucus release. The phospholipase A2 inhibitor, bromophenacyl bromide, and various lipoxygenase inhibitors blocked HNE-stimulated mucus release by 30-40%. The effect of HNE upon mucus release from human upper and lower airways was also examined. HNE stimulated greater mucus release from human bronchi than from nasal mucosa. The cellular source of the mucus was investigated in feline trachea and human upper airway by quantitation of mucus using enzyme assays for a specific mucous cell marker (monoclonal antibody 7F-10). HNE stimulated the release of 7F-10 detectable mucus, and after coincubation with chloromethylketone this stimulation was blocked. These data demonstrate that neutrophil products may alter airway mucus secretion and that altered eicosanoid metabolism may partially mediate these effects. Additionally, the lower airways appear more responsive to HNE than upper airways.
Lundgren
J D
JD
Critical Care Medicine Department, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland.
Rieves
R D
RD
Mullol
J
J
Logun
C
C
Shelhamer
J H
JH
D000818:Animals; D001980:Bronchi / Q000378:metabolism; D056649:Cathepsin G; D002403:Cathepsins / Q000494:pharmacology*; D002415:Cats; D015777:Eicosanoids / Q000378:metabolism; D006801:Humans; D019272:Leukocyte Elastase; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology; D016210:Methacholine Chloride / Q000494:pharmacology; D009093:Mucus / Q000378:metabolism*; D009297:Nasal Mucosa / Q000378:metabolism; D009924:Organ Culture Techniques; D010196:Pancreatic Elastase / Q000494:pharmacology*; D010740:Phospholipases / Q000037:antagonists & inhibitors; D012137:Respiratory System / Q000378:metabolism*; D012697:Serine Endopeptidases; D015842:Serine Proteinase Inhibitors / Q000494:pharmacology; D014132:Trachea / Q000378:metabolism
D015777:Eicosanoids; D016859:Lipoxygenase Inhibitors; D015842:Serine Proteinase Inhibitors; D016210:Methacholine Chloride; D010740:Phospholipases; D002403:Cathepsins; D012697:Serine Endopeptidases; C534094:CTSG protein, human; D056649:Cathepsin G; D010196:Pancreatic Elastase; D019272:Leukocyte Elastase