Protein kinase C-α and arginase I mediate pneumolysin-induced pulmonary endothelial hyperpermeability.

American Journal of Respiratory Cell and Molecular Biology
Rudolf LucasTrinad Chakraborty

Abstract

Antibiotics-induced release of the pore-forming virulence factor pneumolysin (PLY) in patients with pneumococcal pneumonia results in its presence days after lungs are sterile and is a major factor responsible for the induction of permeability edema. Here we sought to identify major mechanisms mediating PLY-induced endothelial dysfunction. We evaluated PLY-induced endothelial hyperpermeability in human lung microvascular endothelial cells (HL-MVECs) and human lung pulmonary artery endothelial cells in vitro and in mice instilled intratracheally with PLY. PLY increases permeability in endothelial monolayers by reducing stable and dynamic microtubule content and modulating VE-cadherin expression. These events, dependent upon an increased calcium influx, are preceded by protein kinase C (PKC)-α activation, perturbation of the RhoA/Rac1 balance, and an increase in myosin light chain phosphorylation. At later time points, PLY treatment increases the expression and activity of arginase in HL-MVECs. Arginase inhibition abrogates and suppresses PLY-induced endothelial barrier dysfunction by restoring NO generation. Consequently, a specific PKC-α inhibitor and the TNF-derived tonoplast intrinsic protein peptide, which blunts PLY-induced...Continue Reading

References

Jan 1, 1995·The Journal of Clinical Investigation·J B RubinsE N Janoff
Apr 1, 1996·American Journal of Respiratory and Critical Care Medicine·J B RubinsE N Janoff
Jan 25, 2000·American Journal of Physiology. Cell Physiology·A A OgonowskiR W Caldwell
Nov 7, 2000·British Journal of Anaesthesia·A L Mundy, K L Dorrington
May 10, 2001·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·C ZhangL Kuo
Sep 25, 2001·Journal of Applied Physiology·S M Dudek, J G Garcia
Nov 2, 2001·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·W J Zhang, B Frei
Jan 4, 2003·Nature Reviews. Immunology·Siamon Gordon
Apr 23, 2003·American Journal of Respiratory Cell and Molecular Biology·Irina PetracheAlexander D Verin
Jul 5, 2003·American Journal of Respiratory and Critical Care Medicine·Nadia EliaRudolf Lucas
Sep 27, 2003·American Journal of Physiology. Heart and Circulatory Physiology·J WaschkeD Drenckhahn
Feb 24, 2004·American Journal of Physiology. Lung Cellular and Molecular Physiology·Louis G ChicoineLeif D Nelin
Mar 31, 2004·Molecular Genetics and Metabolism·Stephen D CederbaumRamaswamy K Iyer
May 4, 2004·American Journal of Physiology. Lung Cellular and Molecular Physiology·Xi-Juan ChenLucky Jain
Jul 9, 2004·The Journal of Immunology : Official Journal of the American Association of Immunologists·Ulrich A MausJürgen Lohmeyer
Sep 15, 2004·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Weiling XuSerpil C Erzurum
Mar 15, 2005·American Journal of Physiology. Lung Cellular and Molecular Physiology·Fei HuangHazel Lum
Aug 12, 2005·American Journal of Physiology. Lung Cellular and Molecular Physiology·Dan PredescuAsrar B Malik
Sep 17, 2005·American Journal of Respiratory and Critical Care Medicine·Hartmut GrasemannFelix Ratjen
May 23, 2006·Critical Care Medicine·Martin WitzenrathHartwig Schütte
Jun 7, 2006·Molecular Genetics and Metabolism·Joshua L DeignanWayne W Grody
Feb 16, 2007·Proceedings of the National Academy of Sciences of the United States of America·Asparouh I IlievFred S Wouters
Sep 25, 2007·Pflügers Archiv : European journal of physiology·Kristina Kusche-VihrogHans Oberleithner
Oct 31, 2007·Circulation Research·Maritza J RomeroRobert W Caldwell
Apr 1, 2008·Annals of the New York Academy of Sciences·Emily VandenbrouckeAsrar B Malik
Jun 12, 2008·Bulletin of the World Health Organization·Igor RudanHarry Campbell
Oct 17, 2008·Molecular Biology of the Cell·Beata Wojciak-StothardJames M Leiper
Jan 13, 2009·British Journal of Pharmacology·N N HuynhK L Andrews
Feb 20, 2009·Microcirculation : the Official Journal of the Microcirculatory Society, Inc·Su WangYuchun Gu
Mar 17, 2009·American Journal of Physiology. Lung Cellular and Molecular Physiology·Michelle L NorthJeremy A Scott
Jan 12, 2010·Vascular Pharmacology·John D CatravasStephen M Black
May 7, 2010·Journal of Biomedicine & Biotechnology·Irina B AlievaAlexander D Verin
Jun 22, 2010·Critical Care Medicine·Janet V DiazMichael A Matthay
Aug 10, 2010·Biochemical and Biophysical Research Communications·Lifen YangFei Yin
Aug 10, 2010·American Journal of Respiratory and Critical Care Medicine·Grant W WatererRichard G Wunderink
Jan 18, 2011·American Journal of Physiology. Lung Cellular and Molecular Physiology·Louis G ChicoineLeif D Nelin
Jul 12, 2011·British Journal of Pharmacology·S ChandraR W Caldwell

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Citations

Feb 8, 2014·PloS One·Feng ChenDavid J R Fulton
Mar 7, 2014·Cell and Tissue Research·Holger C Müller-RedetzkyMartin Witzenrath
Nov 12, 2014·Biochemistry. Biokhimii︠a︡·I B Alieva
Jul 17, 2014·American Journal of Respiratory and Critical Care Medicine·István CzikoraRudolf Lucas
Apr 16, 2015·American Journal of Respiratory Cell and Molecular Biology·Sarah StattCheng-Yuan Kao
Sep 4, 2014·The Journal of Infectious Diseases·Maria LooseHelena Pillich
Feb 16, 2018·American Journal of Respiratory and Critical Care Medicine·Birgitt GutbierUNKNOWN CAPNETZ and PROGRESS Study Groups ‡
Jan 10, 2019·Antioxidants & Redox Signaling·Evgeny A ZemskovStephen M Black
Jan 23, 2018·Frontiers in Immunology·Jürg HamacherUz Stammberger
Apr 15, 2020·Antioxidants & Redox Signaling·Mobarak Abu MraheilRudolf Lucas
Apr 8, 2020·Toxins·Rudolf LucasJürg Hamacher
Mar 23, 2021·JCI Insight·Galina A GusarovaJahar Bhattacharya
Jul 20, 2021·Journal of Cellular Physiology·Jun ZhangZhi-Ren Zhang

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