Effects of cystic fibrosis airway secretions on the rat lung: the role of neutrophil elastase. Rees, Dianne D., and Joseph D. Brain. Physiology Program, Department of Environmental Health, Harvard University School of Public Health, Boston, MA, 02115
APStracts 2:0065L, 1995.
Products of inflammatory cells present in pulmonary secretions may compromise lung structure and function. In order to investigate the pathogenic potential of 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 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 prior to 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 BAL albumin level or neutrophil numbers. Rats treated orally with NE inhibitor prior to 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. 

Received 7 September 1994; accepted in final form 5 April 1995.
APS Manuscript Number L265-4.
Article publication pending Am. J. Physiol. (Lung Cell. Mol.
Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on  2 May 1995.