Epithelial-mesenchymal interactions in postnatal rat lung growth

Abstract

Epithelial-mesenchymal interactions have been implicated in epithelial cell differentiation in fetal lung. The role of such intercellular communication during postnatal lung growth is now evaluated to correlate intercellular contacts with cell division and with biochemical function of epithelial and interstitial cells. Sexed newborn rats, killed at frequent intervals to 8 weeks, received 3H-thymidine 1 h before death. A period of rapid cell proliferation between 3 and 10 days involved a five-fold increase in labeling index of both interstitial and type 2 epithelial cells. Hydroxyproline levels increased rapidly as interstitial cell division slowed, and epithelial growth was associated with elevated levels of disaturated phosphatidylcholine. Compared to the time of birth when epithelial cell division was slow, continuous basement membrane (BM) was more frequently found beneath type 2 cells during the postnatal proliferative phase, and fewer foot processes (FP) penetrated the BM; type 1 cells had few FP and uninterrupted BM. The number of intercellular contacts between type 2 cells and interstitial cells, one per two epithelial cell profiles at birth, decreased rapidly during the postnatal proliferative phase. There was a subsequent increase between 2 and 4 weeks that may reflect postmitotic epithelial differentiation. These observations support the hypothesis that transfer of mesenchymal factors may be important in the control of pulmonary epithelial growth and differentiation. The low incidence of cell-cell contacts seen after 4 weeks, one per five epithelial cell profiles, may reflect base levels of communication necessary to retain type 2 cell function in a resting cell population.