CELLULAR ALTERATIONS IN THE ALVEOLAR WALL IN BLEOMYCIN-INDUCED PULMONARY FIBROSIS IN RATS - AN ULTRASTRUCTURAL MORPHOMETRIC STUDY

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Abstract
This study was designed to measure quantitatively changes in populations of major alveolar cell types, with a particular focus on nonmuscle, contractile interstitial cells, in lungs of rats 14 and 26 days after a single intratracheal instillation of bleomycin sulfate. Standard ultrastructural morphometric techniques, including stratified random sampling, were applied to airway-perfused lungs from bleomycin-instilled and control (saline-instilled) rats. Cell numbers and volumes were calculated for each major cell type populating the pulmonary parenchyma. At 14 days postinstillation, the number and volume of fibroblasts, contractile interstitial cells, Type II epithelial cells, and macrophages were measured significantly. At 28 days, the largest increase was in contractile interstitial cells, approximately tenfold in number and fourfold in volume over control cells. The number and volume of non-filament-containing fibroblasts did not differ between control and treated groups at this time. These data suggest proliferating fibroblasts undergo "differentiation" into cell types with increasing contractile capability during the development of fibrosis in this animal model. This study represents the first quantitative description of increases in contractile interstitial cells related to pulmonary fibrosis.