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10.1016/j.ebiom.2017.08.013 http://scihub22266oqcxt.onion/10.1016/j.ebiom.2017.08.013 C5605378!5605378!28835336     free     free     free Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534       EBioMedicine 2017 ; 23 (ä): 173-84 Nephropedia Template TP {{tp|p=28835336|t=2017. Neutrophil Membrane Cholesterol Content is a Key Factor in Cystic Fibrosis Lung Disease |pdf=|usr=}}{{28835336}} gab.com Text Neutrophil Membrane Cholesterol Content is a Key Factor in Cystic Fibrosis Lung Disease JO: EBioMedicine http://www.kidney.de/pget.php?&tw=1&pmid=28835336 #FOAvip Background: Identification of mechanisms promoting neutrophil trafficking to the lungs of patients with cystic fibrosis (CF) is a challenge for next generation therapeutics. Cholesterol, a structural component of neutrophil plasma membranes influences cell adhesion, a key step in transmigration. The effect of chronic inflammation on neutrophil membrane cholesterol content in patients with CF (PWCF) remains unclear. To address this we examined neutrophils of PWCF to evaluate the cause and consequence of altered membrane cholesterol and identified the effects of lung transplantation and ion channel potentiator therapy on the cellular mechanisms responsible for perturbed membrane cholesterol and increased cell adhesion. Methodology: PWCF homozygous for the ?F508 mutation or heterozygous for the G551D mutation were recruited (n = 48). Membrane protein expression was investigated by mass spectrometry. The effect of lung transplantation or ivacaftor therapy was assessed by ELISAs, and calcium fluorometric and ?-calpain assays. Findings: Membranes of CF neutrophils contain less cholesterol, yet increased integrin CD11b expression, and respond to inflammatory induced endoplasmic reticulum (ER) stress by activating ?-calpain. In vivo and in vitro, increased ?-calpain activity resulted in proteolysis of the membrane cholesterol trafficking protein caveolin-1. The critical role of caveolin-1 for adequate membrane cholesterol content was confirmed in caveolin-1 knock-out mice. Lung transplant therapy or treatment of PWCF with ivacaftor, reduced levels of circulating inflammatory mediators and actuated increased caveolin-1 and membrane cholesterol, with concurrent normalized neutrophil adhesion. Interpretation: Results demonstrate an auxiliary benefit of lung transplant and potentiator therapy, evident by a reduction in circulating inflammation and controlled neutrophil adhesion. Twit Text FOAVip Neutrophil Membrane Cholesterol Content is a Key Factor in Cystic Fibrosis Lung Disease ????EBioMedicine http://www.kidney.de/pget.php?&tw=1&pmid=28835336 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=28835336 #FOAvip English Wikipedia <ref>{{Cite pmid|28835336}}</ref> Neutrophil Membrane Cholesterol Content is a Key Factor in Cystic Fibrosis Lung Disease #MMPMID28835336 White MM; Geraghty P; Hayes E; Cox S; Leitch W; Alfawaz B; Lavelle GM; McElvaney OJ; Flannery R; Keenan J; Meleady P; Henry M; Clynes M; Gunaratnam C; McElvaney NG; Reeves EP EBioMedicine 2017[Sep]; 23 (ä): 173-84 PMID28835336show ga Background: Identification of mechanisms promoting neutrophil trafficking to the lungs of patients with cystic fibrosis (CF) is a challenge for next generation therapeutics. Cholesterol, a structural component of neutrophil plasma membranes influences cell adhesion, a key step in transmigration. The effect of chronic inflammation on neutrophil membrane cholesterol content in patients with CF (PWCF) remains unclear. To address this we examined neutrophils of PWCF to evaluate the cause and consequence of altered membrane cholesterol and identified the effects of lung transplantation and ion channel potentiator therapy on the cellular mechanisms responsible for perturbed membrane cholesterol and increased cell adhesion. Methodology: PWCF homozygous for the ?F508 mutation or heterozygous for the G551D mutation were recruited (n = 48). Membrane protein expression was investigated by mass spectrometry. The effect of lung transplantation or ivacaftor therapy was assessed by ELISAs, and calcium fluorometric and ?-calpain assays. Findings: Membranes of CF neutrophils contain less cholesterol, yet increased integrin CD11b expression, and respond to inflammatory induced endoplasmic reticulum (ER) stress by activating ?-calpain. In vivo and in vitro, increased ?-calpain activity resulted in proteolysis of the membrane cholesterol trafficking protein caveolin-1. The critical role of caveolin-1 for adequate membrane cholesterol content was confirmed in caveolin-1 knock-out mice. Lung transplant therapy or treatment of PWCF with ivacaftor, reduced levels of circulating inflammatory mediators and actuated increased caveolin-1 and membrane cholesterol, with concurrent normalized neutrophil adhesion. Interpretation: Results demonstrate an auxiliary benefit of lung transplant and potentiator therapy, evident by a reduction in circulating inflammation and controlled neutrophil adhesion. äNeutrophil Membrane Cholesterol Content is a Key Factor in Cystic Fibr(epmc).pdf DeepDyve Pubget Overpricing