CELLULAR-LOCALIZATION OF TRANSFORMING GROWTH-FACTOR-BETA EXPRESSION IN BLEOMYCIN-INDUCED PULMONARY FIBROSIS

Bleomycin-induced pulmonary, fibrosis is associated with increased lun g transforming growth factor-beta(TGF-beta) gene expression, but cellu lar localization of the source of this expression has not been unequiv ocally, established In this study, lung fibrosis was induced in rats b y endotracheal bleomycin injection on day 0 and on selected days after wards, lungs were harvested for in situ hybridization, immunohistochem ical and histochemical analyses for TGF-beta(1) mRNA and protein expre ssion, and cell identification The results show that control lungs exp ress essentially no detectable TGF-beta(1) mRNA or protein in the pare nchyma. Before day 3 after bleomycin treatment, scattered bronchiolar epithelial cells, mononuclear cells, and eosinophils expressed elevate d levels of TGF-beta(1). Between days 3 and 14, there was a major incr ease in the number of eosinophils, myofibroblasts, and fibroblasts str ongly expressing TGF-beta(1) mRNA and protein. TGF-beta(1)-producing c ells were predominantly localized within areas of injury and active fi brosis. After day 14, the intensity and number of TGF-beta(1)-expressi ng cells significantly declined and were predominantly found in fibrob lasts in fibrotic areas, The expression of TGF-beta(1) Protein was gen erally coincident with that for mRNA with the exception of bronchiolar epithelial cells in which strong protein expression was unaccompanied by a commensurate increase in mRNA. The study demonstrates that myofi broblasts, fibroblasts, and eosinophils represent the major sources of increased lung TGF-beta(1) expression in this model of pulmonary fibr osis.