title: Sepsis impairs alveolar epithelial function by downregulating Na-K-ATPase pump.
abstract: Widespread vascular endothelial injury is the major mechanism for multiorgan dysfunction in sepsis. Following this process, the permeability of the alveolar capillaries is augmented with subsequent increase in water content and acute respiratory distress syndrome (ARDS). Nevertheless, the role of alveolar epithelium is less known. Therefore, we examined alveolar fluid clearance (AFC) using isolated perfused rat lung model in septic rats without ARDS. Sepsis was induced by ligating and puncturing the cecum with a 21-gauge needle. AFC was examined 24 and 48 h later. The expression of Na-K-ATPase proteins was examined in type II alveolar epithelial cells (ATII) and basolateral membrane (BLM). The rate of AFC in control rats was 0.51 ± 0.02 ml/h (means ± SE) and decreased to 0.3 ± 0.02 and 0.33 ± 0.03 ml/h in 24 and 48 h after sepsis induction, respectively (P < 0.0001). Amiloride, significantly decreased AFC in sepsis; conversely, isoproterenol reversed the inhibitory effect of sepsis. The alveolar-capillary barrier in septic rats was intact; therefore the finding of increased extravascular lung water in early sepsis could be attributed to accumulation of protein-poor fluid. The expression of epithelial sodium channel and Na-K-ATPase proteins in whole ATII cells was not different in both cecal ligation and puncture and control groups; however, the abundance of Na-K-ATPase proteins was significantly decreased in BLMs of ATII cells in sepsis. Early decrease in AFC in remote sepsis is probably related to endocytosis of the Na-K-ATPase proteins from the cell plasma membrane into intracellular pools, with resultant inhibition of active sodium transport in ATII cells.
authors.affiliation: The Research Laboratory for Lung Biology, Department of Physiology and Biophysics, Ruth and Bruce Rappaport Faculty of Medicine, Technion, Israel Institute of Technology, Haifa, Israel.
authors.forename: Gidon
authors.initials: G
authors.lastname: Berger
authors.forename: Julia
authors.initials: J
authors.lastname: Guetta
authors.forename: Geula
authors.initials: G
authors.lastname: Klorin
authors.forename: Reem
authors.initials: R
authors.lastname: Badarneh
authors.forename: Eyal
authors.initials: E
authors.lastname: Braun
authors.forename: Vera
authors.initials: V
authors.lastname: Brod
authors.forename: Niroz Abu
authors.initials: NA
authors.lastname: Saleh
authors.forename: Adriana
authors.initials: A
authors.lastname: Katz
authors.forename: Haim
authors.initials: H
authors.lastname: Bitterman
authors.forename: Zaher S
authors.initials: ZS
authors.lastname: Azzam
mesh_terms: D000584:Amiloride / Q000494:pharmacology; D000818:Animals; D015153:Blotting, Western; D001992:Bronchoalveolar Lavage Fluid; D002395:Catecholamines / Q000097:blood; D015536:Down-Regulation / Q000187:drug effects; D053503:Epithelial Sodium Channels / Q000378:metabolism; D015633:Extravascular Lung Water / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D007150:Immunohistochemistry; D008297:Male; D009929:Organ Size / Q000187:drug effects; D010539:Permeability / Q000187:drug effects; D011650:Pulmonary Alveoli / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018805:Sepsis / Q000097:blood / Q000201:enzymology* / Q000503:physiopathology*; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*
chemical_list: D002395:Catecholamines; D053503:Epithelial Sodium Channels; D000584:Amiloride; D000254:Sodium-Potassium-Exchanging ATPase