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 <5%. Fluid transport is regulated by ion transport, with water movement following passively. Current concepts are that TII cells are the main sites of ion transport in the lung. TI cells have been thought to provide only passive barrier, rather than active, functions. Because TI cells line most of the internal surface area of the lung, we hypothesized that TI cells could be important in the regulation of lung liquid homeostasis. We measured both Na ؉ 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 Ϸ2.5 times that of TII cells. Rb ؉ uptake in TI cells was Ϸ3 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 (␣, ␤, and ␥) of the epithelial sodium channel ENaC and two subunits of Na ؉ -, K ؉ -ATPase. By Western blot analysis, TI cells contain Ϸ3 times the amount of ␣ENaC͞g 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.

Immortalization of Human Alveolar Epithelial Cells to Investigate Nanoparticle Uptake

“…Rat AT1 cells were shown to take up 2.5 times more Na 1 per mg of protein, compared with AT2 cells isolated from the same animals (5). This and other studies suggest that AT1 cells are as important as AT2 cells in lung fluid homoeostasis.…”

“…Recently, AT1 cells have been isolated from rodent lung and have been shown to express the epithelial sodium channel, ENaC, and Na 1 and K 1 ATPase activity and are therefore well equipped to regulate fluid homeostasis (4,5). Rat AT1 cells were shown to take up 2.5 times more Na 1 per mg of protein, compared with AT2 cells isolated from the same animals (5).…”

Resolvin D3 and Aspirin-Triggered Resolvin D3 Are Protective for Injured Epithelia

“…AT-RvD3 administration led to a significant reduction in lung water ( Figure 3A). Because ENaC serves a major role in alveolar water clearance, 21,22 we next measured whole lung expression of the ENaCg subunit ( Figure 3B). Results were quantitated by densitometry and normalized to a-tubulin.…”

The use of alveolar epithelial type I cell-selective markers to investigate lung injury and repair

“…The gas exchange barrier is composed of ATI and endothelial cells joined by fused basement membranes. ATI cells are important in the regulation of alveolar fluid balance and surfactant secretion by ATII cells in response to stretch [7][8][9][10]. ATII cells cover the remaining 2-5% of the lung9s surface area.…”