Alveolar wall basement membranes in bleomycin-induced pulmonary fibrosis

The ultrastructural characteristics of alveolar wall basement membranes (BM) were defined in an experimental model of pulmonary fibrosis. Lungs of adult hamsters were examined 2 to 60 days after a single intratracheal instillation of 0.5 units of bleomycin sulfate. Sections of lung fixed with tannic acid and glutaraldehyde were analyzed for epithelial basement membrane (EPI-BM) thickness and duplication, and tissue incubated in ruthenium red prior to fixation was evaluated for distribution of EPI-BM anionic sites. There were no major alterations in capillary EPI-BM. Six days after bleomycin, during acute inflammation, there was focal injury to alveolar epithelial cells and resultant denudation of EPI-BM. Denuded EPI-BM was folded with the lamina densa 60% thicker than in control animals, suggesting its active or passive retraction. Despite type 2 cell hyperplasia and repopulation of the epithelium, there was no duplication of EPI-BM. Thirty and 60 days after bleomycin, the epithelium was intact, inflammation had subsided, and widespread but focal fibrosis was present. This stage was characterized by thickening and duplication of the EPI-BM; 10% of EPI-BM on the thin side of the alveolar wall were duplicated at 30 days and 30% at 60 days. Duplication and thickening, although worse in fibrotic areas, also occurred in normal-appearing areas of lung, showing that EPI-BM changes may be the only residuum of previous damage. Duplication of EPI-BM in this model of pulmonary fibrosis is a late rather than an early feature of disease.(ABSTRACT TRUNCATED AT 250 WORDS)