MYOFIBROBLASTS AND THEIR ROLE IN LUNG COLLAGEN GENE-EXPRESSION DURINGPULMONARY FIBROSIS - A COMBINED IMMUNOHISTOCHEMICAL AND IN-SITU HYBRIDIZATION STUDY

Appearance of contractile filament-laden stromal cells or myofibroblas ts is a characteristic of lung fibrotic lesions. The role of these cel ls in fibrosis and their cytoskeletal phenotype are not fully, delinea ted. This study was undertaken to further investigate these issues usi ng a model of lung fibrosis. Rats were treated endotracheally with ble omycin on day O, and their lungs examined at various time points by in situ hybridization for alpha(1)(I) procollagen mRNA expression and by immunohistochemistry for desmin and alpha-smooth muscle actin express ion The results show an increase in the number of cells resembling fib roblasts and strongly positive for alpha-smooth muscle actin, desmin a nd procollagen mRNA expression in lungs of animals treated with bleomy cin, with the increase being maximal between clays 7 and 14 after bleo mycin treatment. Two types of newly positive cells could be discerned. The first expressing alpha-smooth muscle actin, desmin, and procollag en mRNA was localized in active fibrotic lesions. Tbe second expressin g only alpha-smooth muscle actin and procollagen mRNA was localized in fibrotic submesothelial areas. Almost all of the newly reactive alpha -smooth muscle actin-positive cells strongly express procollagen mRNA, and they constituted most of the cells actively expressing procollage n. These findings suggest that the newly appearing myofibroblast chara cterized by alpha-smooth muscle actin and/or desmin expression may be responsible for most if not all of the increased lung collagen gene ex pression in pulmonary fibrosis.