Acute Lung Injury Edema Fluid Decreases Net Fluid Transport across Human Alveolar Epithelial Type II Cells

Department of Medicine, Stanford University, Palo Alto, California, United States
Journal of Biological Chemistry (Impact Factor: 4.57). 09/2007; 282(33):24109-19. DOI: 10.1074/jbc.M700821200
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Most patients with acute lung injury (ALI) have reduced alveolar fluid clearance that has been associated with higher mortality. Several mechanisms may contribute to the decrease in alveolar fluid clearance. In this study, we tested the hypothesis that pulmonary edema fluid from patients with ALI might reduce the expression of ion transport genes responsible for vectorial fluid transport in primary cultures of human alveolar epithelial type II cells. Following exposure to ALI pulmonary edema fluid, the gene copy number for the major sodium and chloride transport genes decreased. By Western blot analyses, protein levels of alphaENaC, alpha1Na,K-ATPase, and cystic fibrosis transmembrane conductance regulator decreased as well. In contrast, the gene copy number for several inflammatory cytokines increased markedly. Functional studies demonstrated that net vectorial fluid transport was reduced for human alveolar type II cells exposed to ALI pulmonary edema fluid compared with plasma (0.02 +/- 0.05 versus 1.31 +/- 0.56 microl/cm2/h, p < 0.02). An inhibitor of p38 MAPK phosphorylation (SB202190) partially reversed the effects of the edema fluid on net fluid transport as well as gene and protein expression of the main ion transporters. In summary, alveolar edema fluid from patients with ALI induced a significant reduction in sodium and chloride transport genes and proteins in human alveolar epithelial type II cells, effects that were associated with a decrease in net vectorial fluid transport across human alveolar type II cell monolayers.

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Available from: Xiaohui Fang, Jun 20, 2014
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    • "Investigators have reported that BALF in ALI contains high levels of several pro-inflammatory cytokines, including IL-1β, IL-6, IL-8, TNFα and TGFβ1 [37-39]. Several of these cytokines have been shown to have opposing effects on sodium transport and AFC. "
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    • "Indeed, it has been reported that K + channels could modify ERK signaling [47] [49] [51]. In addition, up-[26] [45] or down-regulation [23] [25] [46] [52] of ENaC expression through ERK1/2 and p38 activation, have been reported, depending on cell types and external stimuli. In fact, many other pathways or signals could be involved in ENaC control by K + channels . "
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    • "Previously, Lee et al. demonstrated that treatment of alveolar epithelial type II cell monolayers with edema fluid from ALI patients altered the expression of transcellular ion channels, impaired fluid clearance, and increased protein flux without altering the staining pattern of the tight junction protein ZO-1 [39]. We hypothesized that differences in MAPk activation, tight junction protein expression, and TER in 2CLP compared to sham was due to signaling molecules secreted by the 2CLP cells in culture. "
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