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 investigate d in several strains of mice with different serum or, proteinase inhib itor levels and PMN lysosomal functions. After an intratracheal instil lation of FMLP (200 mu g), all strains of mice showed a similar PMN in flux in alveolar spaces with an increase (approximately 4- to 5-fold) in bronchoalveolar lavage total cell count, which peaked at 24 to 48 h ours. 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 l ung elastin content (-17% and -37%, respectively) and by the developme nt of significant emphysema (mean linear intercept, +28% and +56%, res pectively). The onset of the pulmonary lesion was preceded by a marked increase of neutrophil elastase burden in alveolar interstitium. Comp ared with NMRI mice, C57BL/6J and pallid mice have lower serum elastas e inhibitory capacity levels. The degree of lung destruction was inver sely correlated with elastase inhibitory capacity levels. Lung elastin degradation and emphysema may be induced by eliciting PMN into the lu ngs only in animals with a deficient anti-elastase screen. Compared wi th C57BL/6J mice, pallid mice showed a significantly greater lung elas tin loss and a higher degree of emphysema after FMLP treatment. These differences may be accounted for by the higher baseline levels of inte rstitial elastase burden. It may be assumed that an enzymatically acti ve elastase was already working on the lung interstitium before FMLP i nstillation in pallid mice.