MECHANICAL DISTENSION MODULATES PULMONARY ALVEOLAR EPITHELIAL PHENOTYPIC-EXPRESSION IN-VITRO

The pulmonary alveolar epithelium is composed of two distinct types of cells, type I and type II cells, both of which are critical for norma l lung function. On the basis of experiments of both nature and in viv o studies, it has been hypothesized that expression of the type I or t ype II phenotype is influenced by mechanical factors. We have investig ated the effects of mechanical distension on the expression of specifi c markers for the type I and type II cell phenotypes in cultured alveo lar type II cells. Rat alveolar type II cells were tonically mechanica lly distended in culture. Cells were analyzed for a marker for the typ e I phenotype (rTI(40), an integral membrane protein specific for type I cells) and for markers for the type II phenotype [surfactant protei n (SP) A, SP-B, and SP-C] as well as for glyceraldehyde-3-phosphate de hydrogenase (GAPDH). Mechanical distension caused a 68 +/- 25% (n = 3) increase in mRNA content of rTI(40) relative to undistended controls. In contrast, mechanical distension resulted in a decrease in mRNA con tent of SP-B to 35 +/- 19% (n = 3) and of SP-C to 20 +/- 6.7% (n = 3) of undistended controls. There was no effect on mRNA. content of SP-A or GAPDH. The differences in mRNA content of SP-B and SP-C were found to be primarily due to changes at the transcriptional level by nuclear run-on assays. The effects on rTI(40) appear to be due to posttranscr iptional events. These data show that mechanical distension influences alveolar epithelial phenotypic expression in vitro, at least in part, at the transcriptional level.