REGULATED STIMULATION OF EPITHELIAL-CELL DNA-SYNTHESIS BY FIBROBLAST-DERIVED MEDIATORS

Interactions of interstitial fibroblasts with nearby epithelial cells are thought to play a role in lung growth and development. The present studies support this premise. Medium conditioned by second-passage lu ng fibroblasts (FCM) stimulated both DNA synthesis and accumulation in low-density (2 X 10(4)/cm(2)) cultures of type II alveolar epithelial cells. FCM effects did not require serum; they were time- and dose de pendent, with half-maximal FCM activity at 1:8 dilution. A maximal res ponse to FCM required 30 h of exposure. FCM: activity was reduced in m edium from fibroblasts treated with dexamethasone, suggesting physiolo gical regulation. Type II cells subjected to cyclic mechanical stress demonstrated an increased response to FCM compared with static culture s. FCM activity did not appear to be accounted for by hepatocyte growt h factor, keratinocyte growth factor, acidic fibroblast growth factor, or fibronectin. These results suggest that early passage lung fibrobl asts release, by regulated pathways, one or more factors that stimulat e DNA synthesis by type II cells. Sensitivity to FCM appears to be ele vated in type II cell cultures subjected to cyclic mechanical stress.