Epithelial-mesenchymal associations of cells in human pulmonary fibrosis and in BHT-oxygen-induced fibrosis in mice.

It was reported earlier that in the lungs of individuals with idiopathic pulmonary fibrosis, many cells lining small air spaces have intimate associations with underlying interstitial cells. The present study confirms and extends these previous observations by describing changes seen in a different patient group. Light microscopy of lung biopsy tissue showed thickened alveolar walls with infiltrates of mixed inflammatory cells. There were undefined associations between interstitial cells and cuboidal and attenuated epithelial cells lining smaller air spaces. Electron microscopy demonstrated that cytoplasmic processes from the lining cells protruded through discontinuities in underlying basement membranes, and that intimate connections between lining cells and interstitial cells frequently were present. In addition, some of the cells lining air spaces had few microvilli, rare pinocytotic vesicles, and did not lie on basement membranes. These cells were mesenchymal-like in appearance and were clearly associated with interstitial cells and connective tissue. Similar pulmonary lesions were observed in mice that received a single intraperitoneal injection of butylated hydroxytoluene and were exposed subsequently to 70% oxygen for 6 days. Our findings suggest that communication between a regenerating epithelium and the underlying mesenchyme is an integral step for ongoing alveolar repair.