Reduction in systemic epithelial ion transport in septicemia-related pulmonary edema due to changes in amiloride-insensitive sodium transport?

Abstract

LETTERS TO THE EDITORReduction in systemic epithelial ion transport in septicemia-related pulmonary edema due to changes in amiloride-insensitive sodium transport?Michael EisenhutMichael EisenhutPublished Online:01 Aug 2008https://doi.org/10.1152/ajplung.90302.2008MoreSectionsPDF (30 KB)Download PDF ToolsExport citationAdd to favoritesGet permissionsTrack citations ShareShare onFacebookTwitterLinkedInEmailWeChat to the editor: In a recent review, O'Brodovich et al. (7) analyzed experimental evidence for the significance of amiloride-insensitive alveolar epithelial sodium transport in the mammalian lung. In a recent observational study of epithelial ion transport in children with meningococcal septicemia-induced pulmonary edema, indirect evidence of a systemic reduction in epithelial sodium transport as evident in sweat glands, salivary gland, and kidneys was found (1). Airway epithelial amiloride-sensitive sodium transport as measured in vivo by nasal potential difference (PD) in ventilated children with septicemia-induced pulmonary edema was, however, not reduced compared with controls. This can be explained by the conclusion of the authors of this review that infection alters amiloride-insensitive pulmonary sodium transport and fluid clearance. The importance of amiloride-insensitive sodium transport has been highlighted by the finding of large numbers of amiloride-insensitive cyclic nucleotide-gated channels in alveolar type I cells, which constitute 95% of the alveolar surface of the lung (4, 6). Likely candidates mediating this reduction in sodium transport are inflammatory mediators (2, 3). Pulmonary edema fluid from patients with lung injury reduced ENaC, α1-Na/K ATPase, and CFTR expression in alveolar type II cells and had increased levels of TNF and IL-1 (5). The more pronounced reduction of CFTR expression and protein levels on the cell surface compared with ENaC and Na/K ATPase may explain our finding of a closer correlation of reduced epithelial chloride transport with respiratory compromise in septicemia-induced pulmonary edema (1). The simultaneous reduction of ENaC expression may explain that sweat sodium levels unlike in cystic fibrosis were higher than sweat chloride levels (1).The fact that there was no evidence of a reduction in systemic potassium transport in children with septicemia-related pulmonary edema may indicate that the ion channels involved are not nonselective cation channels. The strong correlation of parameters relating to sodium transport with those relating to chloride transport in septicemia-related pulmonary edema (1) may either point to a link between dysfunction of amiloride-insensitive sodium transport and CFTR dysfunction or an inhibition of basolateral Na/K ATPase leading to a reduction of both apical amiloride-insensitive sodium transport and CFTR function. Our findings on airway epithelial ion transport may not apply to alveolar epithelial ion transport, but our evidence for a generalized epithelial ion transport derangement suggests that it should reflect the changes. Future research could employ inhibitors of amiloride-insensitive sodium transport in nasal PD measurements in patients with pulmonary edema to gain insight into changes in respiratory epithelial sodium transport in critical illness in vivo.REFERENCES1 Eisenhut M, Wallace H, Barton P, Gaillard E, Newland P, Diver M, Southern KW. Pulmonary edema in meningococcal septicemia associated with reduced epithelial chloride transport. Pediatr Crit Care Med 7: 119–124, 2006.Crossref | PubMed | ISI | Google Scholar2 Eisenhut M. Changes in ion transport in inflammatory disease. J Inflamm 3: 5, 2006.Crossref | Google Scholar3 Eisenhut M. Reduction of alveolar epithelial ion and fluid transport by inflammatory mediators. Am J Respir Cell Mol Biol 36: 388–389, 2007.Crossref | PubMed | ISI | Google Scholar4 Guidot DM, Folkesson HG, Jain L, Sznajder JI, Pittet JF, Matthay MA. Integrating acute lung injury and regulation of alveolar fluid clearance. Am J Physiol Lung Cell Mol Physiol 291: L301–L306, 2006.Link | ISI | Google Scholar5 Lee JW, Fang X, Dolganov G, Fremont RD, Bastarache JA, Ware LB, Matthay MA. Acute lung injury edema fluid decreases net fluid transport across human alveolar epithelial type II cells. J Biol Chem 282: 24109–24119, 2007.Crossref | PubMed | ISI | Google Scholar6 Norlin A, Lu LN, Guggino SE, Matthay MA, Folkesson HG. Contribution of amiloride-insensitive pathways to alveolar fluid clearance in adult rats. J Appl Physiol 90: 1489–1496, 2001.Link | ISI | Google Scholar7 O'Brodovich H, Yang P, Gandhi S, Otulakowski G. Amiloride-insensitive Na+ and fluid absorption in the mammalian distal lung. Am J Physiol Lung Cell Mol Physiol 294: L401–L408, 2008.Link | ISI | Google ScholarAUTHOR NOTESAddress for reprint requests and other correspondence: M. Eisenhut, Luton and Dunstable Hospital NHS Foundation Trust, Lewsey Road, Luton LU40DZ, United Kingdom (e-mail: [email protected]) Download PDF Previous Back to Top FiguresReferencesRelatedInformation More from this issue > Volume 295Issue 2August 2008Pages L378-L378 Copyright & PermissionsCopyright © 2008 the American Physiological Societyhttps://doi.org/10.1152/ajplung.90302.2008PubMed18663249History Published online 1 August 2008 Published in print 1 August 2008 Metrics