Effects of cystic fibrosis airway secretions on rat lung: role of neutrophil elastase.
Products of inflammatory cells present in pulmonary secretions may compromise lung structure and function. To investigate the pathogenic potential of cystic fibrosis (CF) airway secretions, we instilled CF sputum sol into the lungs of healthy rats and measured the resulting lung injury and inflammation. The ability of a neutrophil elastase (NE) inhibitor, L-680,833, to mitigate these responses was also investigated. CF sputum sol instilled into rat lungs induced hemorrhage, an increase in epithelial permeability, and neutrophil recruitment to the airspaces. However, when sputum sol was preincubated with NE inhibitor before instillation, hemorrhage was completely prevented, suggesting that NE within the CF airway secretions was responsible for the observed hemorrhagic injury. NE-inhibitor treatment had no effect on the observed increases in bronchoalveolar lavage albumin level or neutrophil numbers. Rats treated orally with NE inhibitor before instillation of sputum sol were also protected from hemorrhagic injury. These results demonstrate that NE within CF airway secretions causes lung tissue damage and that animals can be protected from such damage with an oral anti-elastase.
Rees
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DD
Department of Environmental Health, Harvard University School of Public Health, Boston, Massachusetts 02115, USA.
Brain
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JD
D000284:Administration, Oral; D000818:Animals; D003550:Cystic Fibrosis / Q000503:physiopathology*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007769:Lactams / Q000494:pharmacology; D019272:Leukocyte Elastase; D008168:Lung / Q000503:physiopathology*; D010196:Pancreatic Elastase / Q000037:antagonists & inhibitors / Q000502:physiology*; D010648:Phenylacetates / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012996:Solutions; D013183:Sputum / Q000502:physiology*
D007769:Lactams; D010648:Phenylacetates; D012996:Solutions; C083284:L 680833; D010196:Pancreatic Elastase; D019272:Leukocyte Elastase