Neutrophil recruitment into the lungs is associated with increased lung elastase burden, decreased lung elastin, and emphysema in alpha 1 proteinase inhibitor-deficient mice.

The possibility that polymorphonuclear leukocytes (PMN) recruited into the lung have the capability to damage alveolar septa was investigated in several strains of mice with different serum alpha 1 proteinase inhibitor levels and PMN lysosomal functions. After an intratracheal instillation of FMLP (200 micrograms), all strains of mice showed a similar PMN influx in alveolar spaces with an increase (approximately 4- to 5-fold) in bronchoalveolar lavage total cell count, which peaked at 24 to 48 hours. At this time, differential cell count in all strains revealed an approximately 40-fold increase in neutrophils. In C57BL/6J and pallid mice but not in NMRI mice, PMN influx was followed by a decrease in lung elastin content (-17% and -37%, respectively) and by the development of significant emphysema (mean linear intercept, +28% and +56%, respectively). The onset of the pulmonary lesion was preceded by a marked increase of neutrophil elastase burden in alveolar interstitium. Compared with NMRI mice, C57BL/6J and pallid mice have lower serum elastase inhibitory capacity levels. The degree of lung destruction was inversely correlated with elastase inhibitory capacity levels. Lung elastin degradation and emphysema may be induced by eliciting PMN into the lungs only in animals with a deficient anti-elastase screen. Compared with C57BL/6J mice, pallid mice showed a significantly greater lung elastin loss and a higher degree of emphysema after FMLP treatment. These differences may be accounted for by the higher baseline levels of interstitial elastase burden. It may be assumed that an enzymatically active elastase was already working on the lung interstitium before FMLP instillation in pallid mice.