REMODELING OF ALVEOLAR WALLS AFTER ELASTASE TREATMENT OF HAMSTERS - RESULTS OF ELASTIN AND COLLAGEN MESSENGER-RNA IN-SITU HYBRIDIZATION

Treatment of hamster lungs with porcine pancreatic elastase (PPE) caus es emphysema and a decrease in lung elastin content, which returns to control level by Day 30. To explore the mechanism of alveolar wall rem odeling after elastolytic injury, we examined the expression of elasti n and alpha(1)(l) collagen mRNAs by in situ hybridization at 1, 2, 3, 5, 7, and 30 d after intratracheal PPE. The lungs of control animals d isplayed weak signals for elastin and alpha(1)(l) collagen mRNA in ple ura, large arteries, veins, and airways. There was little or no signal in respiratory air space walls. Increased expression of elastin and a lpha(1)(l) collagen mRNA began by Day 1 after PPE and reached an asymp tote by Day 3 that was maintained by elastin until Day 7; expression o f alpha(1)(l) collagen mRNA waned earlier. Elastin and, to a lesser ex tent, alpha(1)(l) collagen mRNA were heavily expressed in pleura, bloo d vessels, and airways. Analysis of serial sections showed elastin mes sage was minimal in the walls of respiratory air spaces and when prese nt, at 3, 5, and 7 d, was primarily found at the free margins of alveo lar septa. Collagen message was very sparse in respiratory air space w alls. By 30 d, elastin mRNA expression was reduced but still above con trol levels and emphysema was widespread and severe. Rank score of ela stin mRNA expression in individual subpleural air spaces showed a posi tive correlation with air space size. In conclusion, most expression o f elastin and alpha(1)(l) collagen mRNA occurs in the pleura, airway, and vascular walls. In respiratory air space walls, expression of elas tin mRNAs occurs in damaged tissue at free septal margins.