Effects of cis-hydroxyproline on type II cell development in fetal rat lung.

The role of collagen in pulmonary epithelial cell division and differentiation during lung development was investigated by injecting the proline analogue cis-hydroxy-L-proline (cis-HYP) to timed pregnant rats. Lung weight, DNA and 3H thymidine incorporation were unchanged when compared to controls; epithelial cell division, determined by autoradiography, was also unchanged. However air sac development and phospholipid synthesis by epithelial cells were retarded in cis-HYP treated animals. The percentage of epithelial cells containing lamellar bodies was reduced at days 20-22 of gestation and the level of disaturated phosphatidylcholine (DSPC) was also significantly lower in treated rats. A sex-related difference was not eliminated by cis-HYP treatment, lung maturation was still more rapid in females. Non-dialysable hydroxyproline levels were decreased, and morphologically, less fibrillar collagen was seen at the epithelial-interstitial cell interface, though direct cell-cell contacts were not reduced. The results indicate that the injection of cis-HYP did not alter lung growth, but caused a reduction in fibrillar collagen which was associated with reduced surfactant synthesis by Type II epithelial cells.