ALVEOLAR FIBROSIS AND CAPILLARY ALTERATION IN EXPERIMENTAL PULMONARY SILICOSIS IN RATS

To analyze the evolution of fibrotic and vascular changes in pulmonary silicosis, ultrastructural and immunohistochemical studies were made of the lungs of rats given a single intratracheal injection of silica particles. Early lesions were characterized by accumulations of macrop hages and neutrophils in alveolar lumina and interstitium and by damag e to alveolar capillaries and epithelial cells. The intraluminal masse s of inflammatory cells developed into granulomas and became associate d with myofibroblasts that migrated from the interstitium through the damaged epithelial lining. Type II epithelial cells and bronchiolar cu boidal cells proliferated rapidly to line the intraluminal granulomas, incorporating them into the interstitium. This process mediated the t ransition from intraalveolar fibrosis to interstitial fibrosis. Vascul ar damage was repaired by proliferation and migration of endothelial c ells. Some endothelial cells in alveolar capillaries expressed Factor VIII-related antigen at 2 wk after silica infusion. In normal animals, this feature was present in peribronchiolar but not in alveolar capil laries. Two patterns of endothelial cell migration were shown by stain ing for proliferating-cell nuclear antigen. The first pattern was char acterized by endothelial cells that extended their cytoplasm over pree xisting, denuded basement membranes and replaced necrotic cells in alv eolar capillaries. At 4 mo after injury, some of these cells had devel oped fenestrations. The second pattern consisted of budlike sproutings that developed only in peribronchiolar connective tissue. These obser vations indicate that peribronchiolar vessels are sources for renewal of alveolar capillary endothelium as well as for neovascularization.