Remodeling of alveolar walls after elastase treatment of hamsters. Results of elastin and collagen mRNA in situ hybridization.
Treatment of hamster lungs with porcine pancreatic elastase (PPE) causes emphysema and a decrease in lung elastin content, which returns to control level by Day 30. To explore the mechanism of alveolar wall remodeling after elastolytic injury, we examined the expression of elastin and alpha1(I) collagen mRNAs by in situ hybridization at 1, 2, 3, 5, 7, and 30 d after intratracheal PPE. The lungs of control animals displayed weak signals for elastin and alpha1(I) collagen mRNA in pleura, large arteries, veins, and airways. There was little or no signal in respiratory air space walls. Increased expression of elastin and alpha1(I) collagen mRNA began by Day 1 after PPE and reached an asymptote by Day 3 that was maintained by elastin until Day 7; expression of alpha1(I) collagen mRNA waned earlier. Elastin and, to a lesser extent, alpha1(I) collagen mRNA were heavily expressed in pleura, blood vessels, and airways. Analysis of serial sections showed elastin message was minimal in the walls of respiratory air spaces and when present, at 3, 5, and 7 d, was primarily found at the free margins of alveolar septa. Collagen message was very sparse in respiratory air space walls. By 30 d, elastin mRNA expression was reduced but still above control levels and emphysema was widespread and severe. Rank score of elastin mRNA expression in individual subpleural air spaces showed a positive correlation with air space size. In conclusion, most expression of elastin and alpha1(I) collagen mRNA occurs in the pleura, airway, and vascular walls. In respiratory air space walls, expression of elastin mRNAs occurs in damaged tissue at free septal margins.
Lucey
E C
EC
Boston VA Medical Center and the Pulmonary Center and Biochemistry Department, Boston University School of Medicine, Boston, Massachusetts, USA.
Goldstein
R H
RH
Stone
P J
PJ
Snider
G L
GL
D000818:Animals; D003094:Collagen / Q000096:biosynthesis*; D006224:Cricetinae; D004195:Disease Models, Animal; D004549:Elastin / Q000096:biosynthesis*; D017403:In Situ Hybridization; D008168:Lung / Q000737:chemistry*; D008297:Male; D010196:Pancreatic Elastase; D011650:Pulmonary Alveoli / Q000378:metabolism / Q000473:pathology*; D011656:Pulmonary Emphysema / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000032:analysis*
D012333:RNA, Messenger; D003094:Collagen; D004549:Elastin; D010196:Pancreatic Elastase