RT Journal Article
SR Electronic
T1 Molecular mechanisms are involved in ethanol mediated lung endothelial barrier dysfunction
JF European Respiratory Journal
JO Eur Respir J
FD European Respiratory Society
SP p816
VO 38
IS Suppl 55
A1 Umapathy Siddaramappa
A1 Alexander Verin
YR 2011
UL http://erj.ersjournals.com/content/38/Suppl_55/p816.abstract
AB Recent studies have uncovered a significant but previously unknown correlation between alcohol (ethanol) abuse and the risk of acute respiratory distress syndrome (ARDS) (1). Despite studies aimed at improving outcomes in patients with ARDS, the mortality remains high at > 40%. For those who abuse alcohol, the mortality is even higher, at 65% (2) and, therefore, alcohol abuse causes tens of thousands of excess deaths annually. One of the important functions of lung endothelium is to provide a barrier against the penetration of bacterial toxins in the circulation and endothelial junctional proteins act as a structural barrier against the paracellular permeation (3). We hypothesized that excessive alcohol could negatively regulate the integrity of the lung endothelial barrier and increases the risk during bacterial infections. Our novel preliminary data using human lung microvascular endothelial cells (HLMVEC) demonstrate that ethanol dose-dependently disrupts the EC barrier properties as evidenced by Electric Cell-Substrate Impedance Sensing (ECIS) based transendothelial electrical resistance measurement. Pretreatment of the HLMVEC with LPS and subsequent challenge with ethanol disrupts the tight junctional proteins and increased phosphorylation of Myosin light chain compared to LPS or ethanol alone treatment suggesting an increased damage to the endothelium when one takes alcohol during bacterial infection. We showed that ethanol inhibit the endothelial wound healing process.References:1. Prout, M et al, 2007. Expert Rev Respir Med 1:197-207.2. Boe, D.M et al, 2009. J Leukoc Biol 86:1097-1104.3. Vandenbroucke, E. et al, 2008. Ann N Y Acad Sci 1123:134-145.