EFFECTS OF CYSTIC-FIBROSIS AIRWAY SECRETIONS ON RAT LUNG - ROLE OF NEUTROPHIL ELASTASE

Products of inflammatory cells present in pulmonary secretions may com promise lung structure and function. To investigate the pathogenic pot ential of cystic fibrosis (CF) airway secretions, we instilled CF sput um sol into the lungs of healthy rats and measured the resulting lung injury and inflammation. The ability of a neutrophil elastase (NE) inh ibitor, 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 airspac es. 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 hemo rrhagic injury. NE-inhibitor treatment had no effect on the observed i ncreases 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 demonst rate that NE within CF airway secretions causes lung tissue damage and that animals can be protected from such damage with an oral anti-elas tase.