AJP - Lung Cellular and Molecular Physiology, Vol 269, Issue 2 195-L202, Copyright © 1995 by American Physiological Society
Effects of cystic fibrosis airway secretions on rat lung: role of neutrophil elastase
D. D. Rees and J. D. Brain
Department of Environmental Health, Harvard University School of Public Health, Boston, Massachusetts 02115, USA.
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.
