INDUCTION OF EMPHYSEMA AND BRONCHIAL MUCUS CELL HYPERPLASIA BY INTRATRACHEAL INSTILLATION OF LIPOPOLYSACCHARIDE IN THE HAMSTER

The aim of this study was to determine whether lipopolysaccharide-induced elastase release from recruited neutrophils in the hamster lung would induce emphysema, measured by mean linear intercept (L(m)) and bronchial mucus cell hyperplasia (BMCH), scored in tissue sections stained with periodic acid-Schiff. Lipopolysaccharide (LPS) was instilled transorally twice a week for up to 5 weeks in hamsters. At 4 weeks after seven LPS instillations, L(m) amounted to 87.6 +/- 1.2-mu-m, while it was 68.3 +/- 1.5-mu-m after seven saline instillations (P < 0.01). At 6 months after the sixth LPS instillation, the L(m) of these lungs was 83.3 +/- 1.6-mu-m, indicating irreversible tissue destruction. LPS-treated hamsters showed marked to severe BMCH, which was most evident in large intrapulmonary airways. Instillations of highly selective inhibitor of hamster PMN elastase resulted in 50 per cent inhibition of LPS-induced emphysema. The development of BMCH was inhibited by approximately 35 per cent by this agent. To study the response in time of cellular infiltration after a single LPS instillation, the lungs of groups of four hamsters were lavaged at different time points. PMN recruitment showed peak values at 4 and 48 h after LPS instillation and returned to baseline values at 96 h. Simulataneous intratracheal instillation of LPS and anti-TNF-alpha antiserum resulted in a considerable reduction of neutrophil influx into bronchoalveolar spaces in the first 6 h after instillation.