EVOLUTION OF 3 PATTERNS OF INTRAALVEOLAR FIBROSIS PRODUCED BY BLEOMYCIN IN RATS

In pulmonary fibrosis, it is known that fibrotic changes develop in th e intra-alveolar spaces and that intra-alveolar fibrosis can be classi fied into three patterns, namely intraalveolar buds, mural incorporati on and obliterative changes. In order to clarify the evolution of intr a-alveolar fibrosis, immunohistochemical studies of extracellular matr ix proteins and electron microscopic observations were made of the lun gs of rats given a single intratracheal instillation of bleomycin. Ail three patterns of fibrosis developed in this model. Intra-alveolar bu ds changed into globular lesions with dense collagen deposition, the s urface of which was covered by alveolar epithelium. Electron microscop y revealed that the buds often contained spiraling collagen fibrils an d numerous microfibrils, but not mature elastic fibres, beneath the re generating epithelial lining cells; the epithelial basement membranes were discontinuous. In contrast, mural incorporation and obliterative changes were associated with alveolar structural remodeling. Electron microscopically, these lesions had bundles of normal collagen fibrils, small elastic fibers, and continuous epithelial basement membranes. T hese results indicate that: (i) intra-alveolar buds, that become intra -alveolar collagen globules, with an unusual extracellular matrix, do not contribute to alveolar structural remodelling; and (ii) areas of m ural incorporation and obliterative changes have the usual type of ext racellular matrix and are essential for alveolar structural remodeling .