Epithelial-fibroblast interactions in bleomycin-induced lung injury and repair.

Intercellular communication between epithelial cells and fibroblasts of the alveolar wall contributes to regulatory control of each cell type. We examined whether lung injury and subsequent fibrosis are associated with disturbance of this mutual control system. Rats received bleomycin intratracheally, and after 10 days, when acute epithelial injury occurs, and at 6 weeks, when repair with fibrosis is found, pure populations of type 2 epithelial cells and lung fibroblasts were prepared to study interactions with respect to growth control. Epithelial cells were cultured alone, on a permeable filter over fibroblasts, and in co-culture with fibroblasts. The results showed that the low growth rate of normal epithelial cells increased when cells were exposed to fibroblast supernatants. This effect was also seen using cells from the 10-day bleomycin group, but it was diminished in the group treated for 6 weeks. However, epithelial cells from exposed or control rats did not show increased DNA synthesis when grown in contact with fibroblasts in co-culture. In contrast, fibroblast growth was inhibited when exposed to epithelial cell secretions in control cultures and when using cells from the 10-day bleomycin group. No inhibition of fibroblast growth by epithelial cells was found using cells from the fibrotic lungs. These results suggest that after lung injury by bleomycin, a fibroblast-secreted factor promotes epithelial growth; however, during repair, regenerating epithelial cells lose the ability to inhibit fibro-blast proliferation. These local changes in cellular control at the alveolar wall may be sufficient to produce pulmonary fibrosis.