The role of ¿-,ß-, and ¿-ENaC subunits in distal lung epithelial fluid absorption induced by pulmonary edema fluid

Edema fluid (EF) increases epithelial Na... transport by rat fetal distal lung epithelia (FDLE) and induces net lung fluid absorption in fetal mouse lung explants [Rafii B, Gillie DJ, Sulowski C, Hannam V, Cheung T, Otulakowski G, Barker PM, O'Brodovich H. J Physiol (Lond) 544: 537-548, 2002]. We now show that EF increases fluid absorption across monolayers of rat FDLE in a dose-dependent manner. To study the role of subunits of the epithelial Na... channel (ENaC) in the phenomena, we cultured explants from the distal lungs of 16-day gestational age wild-type (WT) or α-, β-, or ...-ENaC knockout or heterozygote (HT) mice. WT explants cultured in media continuously expanded over time as a result of net fluid secretion. In contrast, when explants were exposed to EF for 24 h, net fluid absorption occurred. EF-exposed explants had normal histology, but marked changes were seen after Triton X-100 or staurosporine exposure. Transmission electron microscopy showed EF promoted lamellar body formation and abundant surfactant in the explants' lumens. EF-induced changes in explant size were similar in α-ENaC knockout, WT, and HT littermate fetal lung explants (P > 0.05). In contrast, EF's effect was attenuated in β- and ...-ENaC knockouts (P < 0.05) vs. WT and HT littermate fetal lung explants. EF exposure slightly decreased or had no effect on mRNA levels for α-ENaC in various mouse genotypes but decreased expression of β- and ...-ENaC subunit mRNAs (P < 0.01) across all genotype groups. We conclude that β- and ...-, but not α-, ENaC subunits are essential for EF to exert its maximal effect on net fluid absorption by distal lung epithelia. (ProQuest: ... denotes formulae/symbols omitted.)