Alveolar epithelial type I cells contain transport proteins and transport sodium, supporting an active role for type I cells in regulation of lung liquid homeostasis

Abstract

Transport of lung liquid is essential for both normal pulmonary physiologic processes and for resolution of pathologic processes. The large internal surface area of the lung is lined by alveolar epithelial type I (TI) and type II (TII) cells; TI cells line >95% of this surface, TII cells + and K⁺ (Rb⁺) transport in TI cells isolated from adult rat lungs and compared the results to those of concomitant experiments with isolated TII cells. TI cells take up Na⁺ in an amiloride-inhibitable fashion, suggesting the presence of Na⁺ channels; TI cell Na⁺ uptake, per microgram of protein, is ≈2.5 times that of TII cells. Rb⁺ uptake in TI cells was ≈3 times that in TII cells and was inhibited by 10⁻⁴ M ouabain, the latter observation suggesting that TI cells exhibit Na⁺-, K⁺-ATPase activity. By immunocytochemical methods, TI cells contain all three subunits (α, β, and γ) of the epithelial sodium channel ENaC and two subunits of Na⁺-, K⁺-ATPase. By Western blot analysis, TI cells contain ≈3 times the amount of αENaC/μg protein of TII cells. Taken together, these studies demonstrate that TI cells not only contain molecular machinery necessary for active ion transport, but also transport ions. These results modify some basic concepts about lung liquid transport, suggesting that TI cells may contribute significantly in maintaining alveolar fluid balance and in resolving airspace edema.