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Membrane traffic in neutrophils and neutrophil-like cells

Bauer, Susanne LU (2006) In Lund University Faculty of Medicine Doctoral Dissertation Series 2006:126.
Abstract
The neutrophil constitutes the first line of defence against invading organisms and its primary function is to recognize, phagocytose and kill intruding microorganisms. In this thesis, the membrane traffic in neutrophils and neutrophil-like cells was studied. Non-opsonised S. pyogenes bacteria was shown to induce a rapid and localised pinosome formation in neutrophils. The pinocytosis was not an inherent feature of phagocytosis and could furthermore be shown to be calcium-dependent. Whereas S. pyogenes bacteria lacking M-proteins induced a pinocytic response, the wild-type M1 strain AP1 was able to modulate membrane traffic and inhibit pinosome formation. Furthermore, the wild-type strain was also shown to selectively inhibit the fusion of... (More)
The neutrophil constitutes the first line of defence against invading organisms and its primary function is to recognize, phagocytose and kill intruding microorganisms. In this thesis, the membrane traffic in neutrophils and neutrophil-like cells was studied. Non-opsonised S. pyogenes bacteria was shown to induce a rapid and localised pinosome formation in neutrophils. The pinocytosis was not an inherent feature of phagocytosis and could furthermore be shown to be calcium-dependent. Whereas S. pyogenes bacteria lacking M-proteins induced a pinocytic response, the wild-type M1 strain AP1 was able to modulate membrane traffic and inhibit pinosome formation. Furthermore, the wild-type strain was also shown to selectively inhibit the fusion of azurophilic granules with phagosomes. To further investigate the importance of other granule types in the killing of S. pyogenes, the HL-60 cell line lacking specific and tertiary granules but possessing azurophilic granules was used. The cell line was shown to be a useful model system when investigating the mechanisms of intracellular survival of S. pyogenes bacteria. Azurophilic granules was furthermore shown to have a major role in killing S. pyogenes in HL-60 cells, whereas oxidative burst only has a limited role.



Membrane traffic in neutrophils is important, not only in the course of bacterial infections and phagocytosis, but also in other diseases. Proteinase 3 ? known to have an important role in the pathogenesis of Wegener's granulomatosis ? and CD177 ? involved in polycythemia vera ? were studied with regards to membrane expression and traffic. Both markers were shown to be co-expressed on the same subset of neutrophils. The proteins were increased in parallel and displayed a dynamic plasma membrane expression with rapid internalization and re-expression. (Less)
Abstract (Swedish)
Popular Abstract in Swedish

Neutrofiler försvarar oss mot sjukdomsframkallande mikroorganismer. Deras primära funktion är att känna igen, fagocytera och avdöda de invaderande mikroorganismerna. I denna avhandling studeras membrantrafik i neutrofiler och neutrofil-lika celler. Här visas att icke-opsoniserade S. pyogenes bakterier inducerar ett snabbt och lokaliserat pinocytossvar hos neutrofiler. Pinocytossvaret är inte förbundet med fagocytos och visades vara kalcium-beroende. Medan S. pyogenes bakterier som saknar M-protein på sin yta inducerar ett pinocytossvar så modulerar vildtypen - AP1 av M1 stammen - membrantrafiken och hämmar pinosombildningen. Vidare visas att vildtypen selektivt hämmar fusion av azurofila granula... (More)
Popular Abstract in Swedish

Neutrofiler försvarar oss mot sjukdomsframkallande mikroorganismer. Deras primära funktion är att känna igen, fagocytera och avdöda de invaderande mikroorganismerna. I denna avhandling studeras membrantrafik i neutrofiler och neutrofil-lika celler. Här visas att icke-opsoniserade S. pyogenes bakterier inducerar ett snabbt och lokaliserat pinocytossvar hos neutrofiler. Pinocytossvaret är inte förbundet med fagocytos och visades vara kalcium-beroende. Medan S. pyogenes bakterier som saknar M-protein på sin yta inducerar ett pinocytossvar så modulerar vildtypen - AP1 av M1 stammen - membrantrafiken och hämmar pinosombildningen. Vidare visas att vildtypen selektivt hämmar fusion av azurofila granula med fagosomer. För att vidare studera vikten av andra granulatyper vad gäller avdödande av S. pyogenes användes HL-60 cell-linjen som saknar specifika och gelatinösa granula men har azurofila granula- Cell-linjen kunde visas vara användbar som modellsystem när mekanismer för intracellulär överlevnad av S. pyogenes bakterier ska studeras. Azurofila granula kunde visas ha den främsta rollen vid avdödande av S. pyogenes bakterier i HL-60 celler medan oxidativ burst bara spelar en underordnad roll.



Membrantrafik hos neutrofiler är viktig, inte bara vid bakteriella infektioner och fagocytos, utan även vid andra sjukdomar. Proteinas 3 ? som har en viktig roll i Wegener's granulomatos ? och CD177 ? bland annat involverad i polycythemia vera ? studerades med avseende på membranuttryck och trafik. Vi kan visa att båda proteinerna uttrycks hos samma subpopulation av neutrofiler. Uttrycksnivån av markörerna påverkas parallelt vid cellaktivering och de båda membranmarkörerna uppvisar ett dynamiskt plasmamembranuttryck med en snabb internalisering och återuttryck på cellytan. (Less)
Please use this url to cite or link to this publication:
author
supervisor
opponent
  • Lundqvist, Helen, Medicinsk mikrobiologi, Molekylär och Klinisk Medicin (IMK), Linköpings Universitet
organization
publishing date
type
Thesis
publication status
published
subject
keywords
Infections, membrane traffic, Hematologi, extracellular fluids, Haematology, Medicin (människa och djur), Medicine (human and vertebrates), CD177, extracellulära vätskor, PR3, phagocytosis, Streptococcus pyogenes, Infektioner, neutrophils
in
Lund University Faculty of Medicine Doctoral Dissertation Series
volume
2006:126
pages
126 pages
publisher
Department of Clinical Sciences, Lund University
defense location
Segerfalksalen, Biomedicinskt Centrum, Sölvegatan 19, Lund.
defense date
2006-11-17 09:15:00
ISSN
1652-8220
ISBN
91-85559-48-2
language
English
LU publication?
yes
additional info
id
ee90aa7e-5895-462b-b071-823e4a1fc051 (old id 547469)
date added to LUP
2016-04-01 16:33:14
date last changed
2019-05-22 01:46:35
@phdthesis{ee90aa7e-5895-462b-b071-823e4a1fc051,
  abstract     = {The neutrophil constitutes the first line of defence against invading organisms and its primary function is to recognize, phagocytose and kill intruding microorganisms. In this thesis, the membrane traffic in neutrophils and neutrophil-like cells was studied. Non-opsonised S. pyogenes bacteria was shown to induce a rapid and localised pinosome formation in neutrophils. The pinocytosis was not an inherent feature of phagocytosis and could furthermore be shown to be calcium-dependent. Whereas S. pyogenes bacteria lacking M-proteins induced a pinocytic response, the wild-type M1 strain AP1 was able to modulate membrane traffic and inhibit pinosome formation. Furthermore, the wild-type strain was also shown to selectively inhibit the fusion of azurophilic granules with phagosomes. To further investigate the importance of other granule types in the killing of S. pyogenes, the HL-60 cell line lacking specific and tertiary granules but possessing azurophilic granules was used. The cell line was shown to be a useful model system when investigating the mechanisms of intracellular survival of S. pyogenes bacteria. Azurophilic granules was furthermore shown to have a major role in killing S. pyogenes in HL-60 cells, whereas oxidative burst only has a limited role.<br/><br>
<br/><br>
Membrane traffic in neutrophils is important, not only in the course of bacterial infections and phagocytosis, but also in other diseases. Proteinase 3 ? known to have an important role in the pathogenesis of Wegener's granulomatosis ? and CD177 ? involved in polycythemia vera ? were studied with regards to membrane expression and traffic. Both markers were shown to be co-expressed on the same subset of neutrophils. The proteins were increased in parallel and displayed a dynamic plasma membrane expression with rapid internalization and re-expression.},
  author       = {Bauer, Susanne},
  isbn         = {91-85559-48-2},
  issn         = {1652-8220},
  language     = {eng},
  publisher    = {Department of Clinical Sciences, Lund University},
  school       = {Lund University},
  series       = {Lund University Faculty of Medicine Doctoral Dissertation Series },
  title        = {Membrane traffic in neutrophils and neutrophil-like cells},
  volume       = {2006:126},
  year         = {2006},
}