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Am. J. Respir. Cell Mol. Biol., Volume 20, Number 2, February, 1999 264-269

Neutrophil Influx into the Lungs of Beige Mice Is Followed by Elastolytic Damage and Emphysema

Eleonora Cavarra, Piero A. Martorana, Margherita de Santi, Barbara Bartalesi, Simone Cortese, Federica Gambelli, and Giuseppe Lungarella

Institute of General Pathology, University of Siena, Siena, Italy; and Cassella AG, Department of Pharmacology, Frankfurt/Main, Germany

The beige mouse is currently used as a model of elastase and cathepsin G deficiency to demonstrate or exclude the role of these proteases in a variety of pathologic conditions. We recently demonstrated that beige cathepsin G is tightly bound to neutrophil lysosomal membranes but is released in near normal quantities during exocytosis. Also, beige neutrophils contain a latent form of elastase that undergoes spontaneous activation when released under in vitro or in vivo conditions. However, the pathogenic potential of this enzyme in matrix degradation has not been ascertained previously. The possibility that in beige mice elastolytic proteases from neutrophils recruited into the lung have the capability to damage alveolar septa was investigated following an intratracheal instillation of N-formyl-L-methionyl-L-leucyl-L-phenylalanine (200 µg). Neutrophil influx was followed by a decrease in lung elastin content (-18%) and by a significant increase of the mean linear intercept (+30%) and of morphologic emphysema. The onset of pulmonary lesion was preceded by a marked increase of neutrophil elastase burden on the alveolar interstitium. The appearance of emphysema was prevented by administration of the serine protease inhibitor 4-(2-aminoetyl)-benzenesulfonyl fluoride hydrochloride (2.4 µg/ml saline). These results demonstrate that the lung elastin degradation and emphysema can occur in beige lungs. The fact that the beige mouse does develop lung elastolytic changes after neutrophil recruitment indicates that this mutant cannot be considered a model of neutrophil function deficiency and used as a model of elastase deficiency.




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Copyright © 1999 American Thoracic Society. 		  ATS Coding and Billing Quarterly