Epithelial cell-fibroblast interactions in lung injury and repair

Although direct intercellular contacts between alveolar epithelial cells and fibroblasts have been described in developing and adult lung, the frequency of such contacts and their relationship to type 2 cell division and differentiation in normal and abnormal repair is not known. The authors now correlate measurements of type 2 cell basal surface, basement membrane continuity, and the incidence of epithelial-interstitial cell contacts with the proliferative index of type 2 cells and fibroblasts in normal repair (after hyperoxia) and in abnormal repair with fibrosis (after bleomycin or butylated hydroxytoluene). In each case, type 1 cell necrosis was followed by an increase in type 2 cell basal surface as the cells spread over the denuded capillary wall before dividing. After hyperoxia, a high but short-lived peak in type 2 cell division was not accompanied by fibrosis. After more severe drug-induced injury, the type 2 proliferative phase was extended and was accompanied by prolonged fibroblast growth. Type 2 cells persisted where they covered a thick interstitium of fibroblasts and fibrillar collagen. The incidence of epithelial-interstitial cell contacts decreased at the time of maximal type 2 cell division, then increased immediately after the peak. The results suggest a reciprocal epithelial-fibroblast control system whereby 1) epithelial necrosis and delayed repair promotes fibroblast growth, and 2) direct contact of epithelial cells with fibroblasts or fibrillar collagen may provide a factor important for the regulation of type 2 cell growth and differentiation.