APOPTOSIS IN THE DEVELOPMENT OF RAT AND HUMAN FETAL LUNGS

The establishment of an effective pulmonary alveolar-capillary interfa ce occurs during mid to late gestation. This requires an expansion of endothelial, epithelial, and air space compartments with relative thin ning of the interstitial compartment. Traditionally, these changes hav e been attributed to differences in the rate of cell growth in the res pective compartments. We hypothesized that apoptosis also participates in this lung remodeling. Using light and electron microscopy, the nuc leosomal ladder pattern of DNA digestion, and the detection of apoptot ic cells ill situ by the TUNEL method (Gavrieli, er al. J. Cell Biol. 1992;119:493-501), we demonstrated the occurrence of apoptosis in feta l lungs in vivo and in explant culture. In the rat fetal lung (RFL) in vivo we detected apoptosis from 16 through 22 d gestation. There was variation in the amount of DNA digestion between fetal lungs, but no c orrelation with gestational age. The findings in human fetal lungs (HF L) from 15 through 24 wk gestation were similar to those of the RFL; t he apoptotic indices for both were about 2 apoptotic cells per thousan d, suggesting that a significant percentage of cells are eliminated by this mechanism. In the HFL explant culture system, a rapid and massiv e wave of apoptosis occurred. In all samples of RFL and HFL examined, apoptosis was restricted to interstitial cells. This work has demonstr ated for the first time that apoptosis is a feature of normal fetal lu ng development and that the process is accelerated in lung explant cul ture.