Killing activity of neutrophils is mediated through activation of proteases by K+ flux

Nature
Emer P ReevesAnthony W Segal

Abstract

According to the hitherto accepted view, neutrophils kill ingested microorganisms by subjecting them to high concentrations of highly toxic reactive oxygen species (ROS) and bringing about myeloperoxidase-catalysed halogenation. We show here that this simple scheme, which for many years has served as a satisfactory working hypothesis, is inadequate. We find that mice made deficient in neutrophil-granule proteases but normal in respect of superoxide production and iodinating capacity, are unable to resist staphylococcal and candidal infections. We also show that activation provokes the influx of an enormous concentration of ROS into the endocytic vacuole. The resulting accumulation of anionic charge is compensated for by a surge of K+ ions that cross the membrane in a pH-dependent manner. The consequent rise in ionic strength engenders the release of cationic granule proteins, including elastase and cathepsin G, from the anionic sulphated proteoglycan matrix. We show that it is the proteases, thus activated, that are primarily responsible for the destruction of the bacteria.

References

Apr 1, 1979·FEBS Letters·A W Segal, T Meshulam
Nov 1, 1975·The Journal of Clinical Investigation·H Odeberg, I Olsson
Oct 16, 1978·Biochemical and Biophysical Research Communications·A W Segal, S B Coade
Dec 1, 1991·Proceedings of the National Academy of Sciences of the United States of America·A Nanda, S Grinstein
Dec 11, 1990·Biochimica Et Biophysica Acta·S O Kolset, J T Gallagher
Nov 27, 1987·Biochimica Et Biophysica Acta·C InceP C Leijh
Mar 1, 1973·The Journal of Clinical Investigation·B M BabiorJ T Curnutte
Oct 1, 1971·The Journal of Clinical Investigation·S J Klebanoff, S H Pincus
Nov 22, 1982·FEBS Letters·B Styrt, M S Klempner
Jan 1, 1981·Methods in Enzymology·A J Barrett
Oct 21, 1994·Biochimica Et Biophysica Acta·A J ThrasherA W Segal
Jul 1, 1996·Experimental Physiology·B J AmosC D Richards
Jun 8, 1999·Annual Review of Immunology·A Aderem, D M Underhill
Dec 1, 1999·The Journal of General Physiology·L M Henderson, R W Meech
Apr 18, 2000·Infection and Immunity·I Guérin, C de Chastellier
May 24, 2000·Proceedings of the National Academy of Sciences of the United States of America·T E DeCourseyL L Thomas
Aug 16, 2000·American Journal of Physiology. Cell Physiology·S B RizoliA Kapus
Nov 23, 2000·The Journal of Biological Chemistry·R SadirH Lortat-Jacob
Feb 22, 2001·The Journal of Clinical Investigation·M L BrennanA J Lusis
Jun 5, 2001·The Journal of Biological Chemistry·A MaturanaN Demaurex
Jul 31, 2001·The Journal of Biological Chemistry·T E DeCourseyM C Dinauer
Aug 22, 2001·Biochemistry·A J Kettle, C C Winterbourn

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Citations

Nov 15, 2002·European Journal of Immunology·Michael MorrPeter F Mühlradt
Aug 5, 2003·BioFactors·Martine Torres, Henry Jay Forman
Feb 12, 2011·Archivum Immunologiae Et Therapiae Experimentalis·Elaine HayesEmer P Reeves
May 25, 2007·Inflammation Research : Official Journal of the European Histamine Research Society ... [et Al.]·D J B MarksA W Segal
May 9, 2008·Cellular and Molecular Life Sciences : CMLS·T E DeCoursey
Jul 31, 2009·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Oliver Soehnlein
Dec 31, 2011·Molecules and Cells·Yun Soo BaeYoung Do Yoo
May 14, 2009·Clinical Reviews in Allergy & Immunology·Daniel J B MarksAnthony W Segal
Jun 9, 2009·Clinical Reviews in Allergy & Immunology·Steven M Holland
May 5, 2005·Fungal Genetics and Biology : FG & B·Vicki HaedensPhilippe Silar
Mar 24, 2004·Current Opinion in Microbiology·Anne Mayer-SchollArturo Zychlinsky
Nov 14, 2003·Microbes and Infection·Dirk RoosChristof Meischl
Nov 14, 2003·Microbes and Infection·Theo J Moraes, Gregory P Downey
Nov 14, 2003·Microbes and Infection·Scott D KobayashiFrank R DeLeo
Nov 14, 2003·Microbes and Infection·Warren L LeeSergio Grinstein
Jun 9, 2005·Current Opinion in Plant Biology·Miguel Angel Torres, Jeffery L Dangl
Mar 22, 2003·Current Opinion in Cell Biology·Toren Finkel
Dec 7, 2002·Microbes and Infection·Abderrazzaq Belaaouaj
Feb 5, 2011·Cell Death and Differentiation·Q RemijsenT Vanden Berghe
Apr 4, 2003·Nature·Thomas E DeCourseyVladimir V Cherny
Feb 27, 2004·Nature·Jatinder AhluwaliaAnthony W Segal
Aug 22, 2006·Nature Cell Biology·Anke DiDeborah J Nelson
Apr 19, 2008·Nature Chemical Biology·Christine C Winterbourn
Mar 25, 2004·Nature Reviews. Immunology·J David Lambeth
Feb 25, 2006·Nature Reviews. Immunology·Carl Nathan
Jun 27, 2006·Nature Reviews. Immunology·Christine T N Pham
Sep 21, 2004·Nature Reviews. Microbiology·Ferric C Fang
May 20, 2006·Nature Reviews. Microbiology·Neeraj ChauhanRichard Calderone
Dec 15, 2007·Nature Reviews. Microbiology·Mihai G NeteaNeil A R Gow
Apr 17, 2009·Nature Reviews. Microbiology·Ronald S FlannaganSergio Grinstein
Jul 9, 2003·Kidney International·Robert DeicherWalter H Hörl
May 1, 2009·The New England Journal of Medicine·Brahm H Segal
Oct 8, 2008·Proceedings of the National Academy of Sciences of the United States of America·Nicholas R WaterfieldRichard H Ffrench-Constant
Oct 7, 2009·Proceedings of the National Academy of Sciences of the United States of America·Deri MorganThomas E DeCoursey
Oct 17, 2009·Proceedings of the National Academy of Sciences of the United States of America·Henry RosenXiaoyun Fu
Aug 23, 2005·Medical Mycology·N G AlmyroudisB H Segal
Mar 20, 2009·Medical Mycology·Brahm H Segal, Luigina R Romani

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