Alterations in blood leukocytes of G551D-bearing cystic fibrosis patients undergoing treatment with ivacaftor

Journal of Cystic Fibrosis : Official Journal of the European Cystic Fibrosis Society
Preston E BratcherAmit Gaggar

Abstract

Ivacaftor improves clinical outcome by potentiation of mutant G551D CFTR. Due to the presence of CFTR in monocytes and polymorphonuclear neutrophils (PMNs), we hypothesized that ivacaftor may impact leukocyte activation. We examined blood leukocytes from G551D CF subjects prior to and at one and six months after receiving ivacaftor. Blood leukocytes from ivacaftor-naïve G551D, F508del, and healthy controls were also treated with ivacaftor ex vivo to assess mutation-specific effects. Compared to healthy controls, G551D CF subjects had significantly higher expression of active CD11b on PMNs and of CD63 on monocytes, which were normalized by in vivo ivacaftor treatment. Ex vivo exposure to ivacaftor of blood cells from G551D, but not F508del and healthy subjects, resulted in changes in CXCR2 and CD16 expression on PMNs. In vivo and ex vivo exposure of G551D CF leukocytes to ivacaftor resulted in an altered activation profile, suggesting mutation-specific leukocyte modulation.

References

Apr 24, 1992·Science·N A BradburyK L Kirk
Jan 1, 1983·Proceedings of the National Academy of Sciences of the United States of America·J E NiedelG R Vandenbark
Mar 19, 2004·The Journal of Biological Chemistry·Jeremy J RoseSundararajan Venkatesan
Mar 11, 2005·Journal of Clinical Gastroenterology·Nelson L Turcios
May 13, 2005·The New England Journal of Medicine·Steven M RoweEric J Sorscher
Jun 15, 2007·Physiology·Paul M Quinton
Oct 23, 2009·British Journal of Pharmacology·Catherine M Greene, Noel G McElvaney
Jan 22, 2010·Journal of Leukocyte Biology·Richard G PainterGuoshun Wang
Mar 23, 2010·Cell·Kate Schroder, Jurg Tschopp
Jun 24, 2010·Journal of Cystic Fibrosis : Official Journal of the European Cystic Fibrosis Society·Brian S MurphyDavid J Feola
Nov 19, 2010·The New England Journal of Medicine·Frank J AccursoBonnie W Ramsey
Nov 4, 2011·The New England Journal of Medicine·Bonnie W RamseyUNKNOWN VX08-770-102 Study Group
Apr 7, 2012·Nature Medicine·Taylor Sitarik Cohen, Alice Prince
Sep 6, 2013·Therapeutic Advances in Respiratory Disease·Kavitha Kotha, John P Clancy
Feb 6, 2014·The International Journal of Biochemistry & Cell Biology·N RieberD Hartl
Mar 19, 2014·Journal of Cystic Fibrosis : Official Journal of the European Cystic Fibrosis Society·Michael J BrowningErol A Gaillard

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Citations

Jun 25, 2016·BioMed Research International·Gillian M LavelleEmer P Reeves
Sep 17, 2017·Thorax·Robert D GrayDonald J Davidson
Jun 26, 2018·American Journal of Respiratory and Critical Care Medicine·Frédéric VelardBarry Plant
Oct 30, 2019·Annals of the American Thoracic Society·Valentine SergeevBradley S Quon
Feb 9, 2016·Biological Chemistry·Julie LavalDominik Hartl
Jul 14, 2016·Journal of Leukocyte Biology·Hang Pong NgGuoshun Wang
Nov 22, 2016·Molecular and Cellular Pediatrics·Camilla Margaroli, Rabindra Tirouvanziam
Aug 14, 2018·Expert Opinion on Pharmacotherapy·Jane C Davies, Isaac Martin
May 6, 2020·Cellular and Molecular Life Sciences : CMLS·Samuel Lara-ReynaMichael F McDermott
Sep 6, 2020·International Journal of Molecular Sciences·Karen KeownClifford C Taggart
Jun 16, 2017·American Journal of Respiratory and Critical Care Medicine·Timothy J Kidd
Sep 8, 2017·Pediatric Pulmonology·Jennifer GuimbellotSteven M Rowe
Aug 29, 2020·The European Respiratory Journal·Gareth R HardistyRobert D Gray
Jul 25, 2021·International Journal of Molecular Sciences·Kiera H HarwoodElena K Schneider-Futschik

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