The Expression of Water and Ion Channels in Diffuse Alveolar Damage Is Not Dependent on DAD Etiology

PLoS One. 2016 Nov 11;11(11):e0166184. doi: 10.1371/journal.pone.0166184. eCollection 2016.

Abstract

Introduction: Aquaporins and ion channels are membrane proteins that facilitate the rapid movement of water and solutes across biological membranes. Experimental and in vitro studies reported that the function of these channels and pulmonary edema resolution are impaired in acute lung injury (ALI). Although current evidence indicates that alveolar fluid clearance is impaired in patients with ALI/diffuse alveolar damage (DAD), few human studies have addressed the alterations in pulmonary channels in this clinical condition. Additionally, it is not known whether the primary cause of DAD is a relevant variable for the channel dysfunction.

Methods: Autopsied lungs of 43 patients with acute respiratory failure (ARF) due to DAD of three different etiologies, non-pulmonary sepsis, H1N1 viral infection and leptospirosis, were compared to 18 normal lungs. We quantified the expression of aquaporin (AQP) 1, AQP3, AQP5, epithelial Na+ channel (ENaC) and sodium potassium ATPase (Na-K-ATPase) in the alveolar septum using immunohistochemistry and image analysis.

Results: The DAD group presented with increased expression of AQP3, AQP5 and Na-K-ATPase and decreased expression of ENaC compared to controls. However, there was no difference in protein expression within the DAD groups of different etiologies.

Conclusion: Water and ion channels are altered in patients with ARF due to DAD. The cause of DAD does not seem to influence the level of impairment of these channels.

MeSH terms

  • Acute Lung Injury / etiology
  • Acute Lung Injury / metabolism
  • Adult
  • Aged
  • Aged, 80 and over
  • Aquaporin 1 / metabolism*
  • Aquaporin 3 / metabolism
  • Aquaporin 5 / metabolism*
  • Autopsy
  • Epithelial Sodium Channels / metabolism*
  • Female
  • Humans
  • Immunohistochemistry
  • Influenza A Virus, H1N1 Subtype / physiology
  • Influenza, Human / complications
  • Influenza, Human / virology
  • Leptospirosis / complications
  • Male
  • Middle Aged
  • Pulmonary Alveoli / metabolism*
  • Pulmonary Alveoli / pathology
  • Respiration Disorders / etiology
  • Respiration Disorders / metabolism
  • Sepsis / complications
  • Sodium-Potassium-Exchanging ATPase / metabolism*
  • Young Adult

Substances

  • AQP1 protein, human
  • AQP3 protein, human
  • AQP5 protein, human
  • Aquaporin 5
  • Epithelial Sodium Channels
  • Aquaporin 1
  • Aquaporin 3
  • Sodium-Potassium-Exchanging ATPase

Grants and funding

This study was funded by Laboratório de Investigação Médica (LIM) 05 da Faculdade de Medicina da Universidade de São Paulo (FMUSP). Thais Mauad and Marisa Dolhnikoff are funded by Conselho Nacional de desenvolvimento Científico e Tecnológico (CNPQ). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.