Evolution of metaplastic squamous cells of alveolar walls in pulmonary fibrosis produced by paraquat. An ultrastructural and immunohistochemical study.

Sequential histologic, ultrastructural, immunohistochemical and morphometric studies were made of the evolutional changes of metaplastic and regenerating alveolar epithelial cells in monkeys from 3 days to 8 weeks after paraquat administration. In the early proliferative phase, many alveoli were lined by single-layered and stratified squamous epithelium and bronchiolized epithelium (i.e., presumably derived from bronchi and bronchioles). The regenerating epithelial cells had well developed bundles of actin-like filaments, which were arranged parallel to the basal surfaces of the cells and were associated with zonulae adherentes; these cells also had intermediate filaments and some desmosomes, but lacked basement membranes, hemidesmosomes and anchoring fibrils. They covered either denuded, wavy and disrupted original epithelial basement membranes or areas of developing intraalveolar fibrosis. In zones of squamous epithelial cell metaplasia associated with intraalveolar fibrosis, fibronexus-like structures appeared to be responsible for the initial adhesion of the cells to the underlying connective tissue. In later phases, single-layered and stratified squamous epithelial cells disappeared, and only bronchiolized epithelial cells, with hemidesmosomes and anchoring fibrils on their basal surfaces, were found in fibrotic alveoli. Although bronchiolized and squamous metaplastic epithelial cells are generally thought to be formed as late events in pulmonary damage, such cells play an important role in early, temporary repair of damaged alveoli.