Lasti Erfinanda, Lin Zou, Birgitt Gutbier, Laura Kneller, Sarah Weidenfeld, Laura Michalick, Disi Lei, Katrin Reppe, Luiz Gustavo Teixeira Alves, Bill Schneider, Qi Zhang, Caihong Li, Diana Fatykhova, Paul Schneider, Wolfgang Liedtke, Eisei Sohara, Timothy J Mitchell, Achim D Gruber, Andreas Hocke, Stefan Hippenstiel, Norbert Suttorp, Andrea Olschewski, Marcus A Mall, Martin Witzenrath, Wolfgang M Kuebler
Pneumonia is the most common cause of the acute respiratory distress syndrome (ARDS). Here, we identified loss of endothelial cystic fibrosis transmembrane conductance regulator (CFTR) as an important pathomechanism leading to lung barrier failure in pneumonia-induced ARDS. CFTR was down-regulated after Streptococcus pneumoniae infection ex vivo or in vivo in human or murine lung tissue, respectively. Analysis of isolated perfused rat lungs revealed that CFTR inhibition increased endothelial permeability in parallel with intracellular chloride ion and calcium ion concentrations ([Cl- ] i and [Ca2+ ] i )...
December 7, 2022: Science Translational Medicine