Prostaglandins stimulate fluid secretion in human fetal lung.

Fluid secretion by the fetal pulmonary epithelium is thought to be important for normal lung development yet little is known about factors regulating its production. As prostaglandins are synthesized in human fetal lung and stimulate secretion in a variety of epithelia, we investigated the effect of prostaglandins E2 and F2a (PGE2 and PGF2 alpha) on ion transport and fluid secretion in cultured first trimester human fetal lung tissue explants. We used conventional microelectrodes to continuously record the transepithelial potential difference (psi t). The addition of either PGE2 or PGF2 alpha to the bathing solution significantly hyperpolarized the lumen negative psi t and the subsequent addition of bumetanide, an inhibitor of chloride secretion in other systems, depolarized psi t by approximately 60% suggesting chloride transport contributed to the voltage. To assess whether this acute change in psi t represented stimulation of fluid secretion, we measured the change in luminal area of the explants after a 24-h exposure to prostaglandins. Both PGE2 and PGF2 alpha caused significant increases in the mean % luminal area of the explants compared with control tissues consistent with a stimulation of lung fluid secretion. Cultured lung tissue explants produced prostaglandins E2 and F2 alpha as assessed by radioimmunoassay of cell culture media samples and both prostaglandins stimulated cAMP accumulation in the explants. These findings show that lung fluid secretion in the human fetal pulmonary epithelium can be stimulated by prostaglandins. This effect may be mediated through cAMP dependent pathways. Prostaglandins may play a physiologic role in regulation of fetal lung fluid transport in vivo.