Increased lung expansion alters the proportions of type I and type II alveolar epithelial cells in fetal sheep

Type I and type II alveolar epithelial cells (AECs) are derived from the sa me progenitor cell, but little is known about the factors that regulate the ir differentiation into separate phenotypes. An alteration in lung expansio n alters the proportion type II AECs in the fetal lung, indicating that thi s may be a regulatory factor. Our aim was to quantify the changes in the pr oportion of type I and type II AECs caused by increased fetal lung expansio n and to provide evidence for transdifferentiation of type II into type I c ells. Lung tissue samples were collected from ovine fetuses exposed to incr eased lung expansion induced by 2, 4, or 10 days of tracheal obstruction (T O). The identities and proportions of AEC types were determined with electr on microscopy. The proportion of type II cells was reduced from 28.5 +/- 2. 2% in control fetuses to 9.4 +/- 2.3% at 2 days of TO and then to 1.9 +/- 0 .8% at 10 days. The proportion of type I AECs was not altered at 2 days of TO (63.1 +/- 2.3%) compared with that of control cells (64.8 +/- 0.5%) but was markedly elevated (to 89.4 +/- 0.9%) at 10 days of TO. The proportion o f an intermediate AEC type, which displayed characteristics of both type I and type II cells, increased from 5.7 +/- 1.3% in control fetuses to 23.8 /- 5.1% by 2 days of TO and was similar to control values at 10 days of TO (7.7 +/- 0.9%). Our data show that increases in fetal lung expansion cause time-dependent changes in the proportion of AEC types, including a transien t increase in an intermediate cell type. These data provide the first evide nce to support the hypothesis that increases in fetal lung expansion induce differentiation of type II into type I AECs via an intermediate cell type.