Rat and hamster species differences in susceptibility to elastase-induced pulmonary emphysema relate to differences in elastase inhibitory capacity

Abstract

Syrian Golden hamsters develop severe emphysema after a single intratracheal dose of elastase, whereas Sprague-Dawley rats exhibit mild emphysema with the same dose per kilogram body weight. We hypothesized that the development of severe emphysema is prevented in rats by the high serum level of alpha1-antitrypsin reported in rats, compared with hamsters, which provides for a high lung elastase inhibitory capacity (EIC). To explore this possibility, we challenged the antiprotease system of the rats by treating them with three similar weekly doses of elastase. Four months after treatment, we evaluated changes in histology, volume, and elastic properties of rat lungs and compared them with those of hamsters receiving a single dose of elastase. We also measured serum alpha1-antitrypsin levels and serum and lung EIC in control rats and hamsters. Results showed that, in association with 40% less serum and lung EIC compared with rats (P < 0.001), hamster lungs had upper-lobe bullae formation, severe microscopic emphysema, a fourfold increase in lung volume (P < 0.01) and a threefold increase in constant k, an index of compliance, of the lung deflation pressure-volume curve (P < 0.01). In contrast, rats developed mild emphysema, with only 50% increase in volume (P < 0.05) and 60% increase in constant k (P < 0.01). In conclusion, two species that differ in serum and lung EIC exhibit significant differences in emphysema development after elastase. Rats with high EIC, despite receiving three doses of elastase, showed significantly less derangement of morphological and physiological parameters than hamsters with low EIC receiving a single dose.