DIFFERENTIAL EXPRESSION OF ELASTIN AND ALPHA(1)(I) COLLAGEN MESSENGER-RNA IN MICE WITH BLEOMYCIN-INDUCED PULMONARY FIBROSIS

Interstitial pulmonary fibrosis is characterized by increased producti on of connective tissue components, including collagen and elastin. Th e role of elastin turnover in pulmonary fibrosis is not clear, and it is not known whether elastin and collagen are regulated separately or together during the inflammatory process. Mice with bleomycin-induced pulmonary fibrosis were investigated to determine the temporal and spa tial changes in localization of elastin mRNA expression, as well as to compare elastin mRNA expression with that of alpha(1)(I) collagen mRN A expression. In control (saline-treated) lungs, elastin mRNA was dete cted by in situ hybridization in arterial walls. No signal was found i n alveolar or airway walls or in pleura; alpha(1)(I) collagen mRNA was detected in the tissue underlying the airway epithelium. An increase in elastin mRNA expression in muscular arteries was observed 3 days af ter bleomycin instillation. Expression was also seen in the adventitia of terminal airways and adjacent small blood vessels. Expression of a lpha(1)(I) collagen mRNA increased in the tissue underlying the airway epithelium. In the pleura, alpha(1)(I) collagen mRNA expression was f ound, although no pleural thickening was evident. The alpha(1)(I) coll agen mRNA expression was particularly increased in the adventitia of t erminal airways and in associated small blood vessels. Obvious in area s of fibrosis, elastin mRNA expression was occasionally increased in t he pleura and airway wall 7 days after bleomycin treatment; alpha(1)(I ) collagen mRNA expression was generally stronger than elastin mRNA ex pression in areas of fibrosis and was frequently intense in the advent itia of airways and associated blood vessels. The fibrotic areas showe d increased elastin mRNA expression 14 and 30 days after bleomycin tre atment. The arteries in fibrotic areas showed normal elastin mRNA leve ls. In the areas of fibrosis and in the adventitia of airways and adja cent blood vessels, alpha(1)(I) collagen mRNA expression was very high . In conclusion, lung elastin biosynthesis is markedly altered by bleo mycin treatment. The localization and intensity of elastin mRNA expres sion is different from the expression of alpha(1)(I) collagen mRNA.