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

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 emphyse...