Membrane traffic in neutrophils and neutrophil-like cells

Susanne Bauer

Membrane traffic in neutrophils and neutrophil-like cells

Susanne Bauer

Infektionsmedicin

Forskningsoutput: Avhandling › Doktorsavhandling (sammanläggning)

Sammanfattning

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.

Originalspråk	engelska
Kvalifikation	Doktor
Tilldelande institution	Infektionsmedicin
Handledare	Tapper, Hans, handledare Björck, Lars, handledare
Tilldelningsdatum	2006 nov. 17
Förlag	Department of Clinical Sciences, Lund University
ISBN (tryckt)	91-85559-48-2
Status	Published - 2006

Bibliografisk information

Defence details

Date: 2006-11-17
Time: 09:15
Place: Segerfalksalen, Biomedicinskt Centrum, Sölvegatan 19, Lund.

External reviewer(s)

Name: Lundqvist, Helen
Title: [unknown]
Affiliation: Medicinsk mikrobiologi, Molekylär och Klinisk Medicin (IMK), Linköpings Universitet

---

<div class="article_info">S Bauer and H Tapper. <span class="article_issue_date">2004</span>. <span class="article_title">Membrane retrieval in neutrophils during phagocytosis: inhibition by M protein-expressing S. pyogenes bacteria.</span> <span class="journal_series_title">J. Leukoc. Biol.</span>, <span class="journal_volume">vol 76</span> <span class="journal_pages">pp 1142-1150</span>.</div>
<div class="article_info">L Staali, S Bauer, M Mörgelin, L Björck and H Tapper. <span class="article_issue_date">2006</span>. <span class="article_title">Streptococcus pyogenes bacteria modulate membrane traffic in human neutrophils and selectively inhibit azurophilic granule fusion with phagosomes.</span> <span class="journal_series_title">Cell. Microbiol.</span>, <span class="journal_volume">vol 8</span> <span class="journal_pages">pp 690-703</span>.</div>
<div class="article_info">S Bauer, P Lönnbro, P Nordenfelt and H Tapper. <span class="article_issue_date">2006</span>. <span class="article_title">S. pyogenes bacteria survive in neutrophil-differentiated HL-60 cells by inhibiting the fusion of azurophilic granules with phagosomes.</span> (manuscript)</div>
<div class="article_info">S Bauer, M Abdgawad, L Gunnarsson, M Segelmark, H Tapper and T Hellmark. <span class="article_issue_date">2006</span>. <span class="article_title">Proteinase 3 and CD177 are expressed on the plasma membrane of the same subset of neutrophils.</span> <span class="journal_series_title">J. Leukoc. Biol.</span>, (accepted)</div>

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Infektionsmedicin

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@phdthesis{ee90aa7e5895462bb071823e4a1fc051,

title = "Membrane traffic in neutrophils and neutrophil-like cells",

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. 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.",

keywords = "Infections, membrane traffic, Hematologi, extracellular fluids, Haematology, Medicin (m{\"a}nniska och djur), Medicine (human and vertebrates), CD177, extracellul{\"a}ra v{\"a}tskor, PR3, phagocytosis, Streptococcus pyogenes, Infektioner, neutrophils",

author = "Susanne Bauer",

note = "Defence details Date: 2006-11-17 Time: 09:15 Place: Segerfalksalen, Biomedicinskt Centrum, S{\"o}lvegatan 19, Lund. External reviewer(s) Name: Lundqvist, Helen Title: [unknown] Affiliation: Medicinsk mikrobiologi, Molekyl{\"a}r och Klinisk Medicin (IMK), Link{\"o}pings Universitet --- <div class={"}article_info{"}>S Bauer and H Tapper. <span class={"}article_issue_date{"}>2004</span>. <span class={"}article_title{"}>Membrane retrieval in neutrophils during phagocytosis: inhibition by M protein-expressing S. pyogenes bacteria.</span> <span class={"}journal_series_title{"}>J. Leukoc. Biol.</span>, <span class={"}journal_volume{"}>vol 76</span> <span class={"}journal_pages{"}>pp 1142-1150</span>.</div> <div class={"}article_info{"}>L Staali, S Bauer, M M{\"o}rgelin, L Bj{\"o}rck and H Tapper. <span class={"}article_issue_date{"}>2006</span>. <span class={"}article_title{"}>Streptococcus pyogenes bacteria modulate membrane traffic in human neutrophils and selectively inhibit azurophilic granule fusion with phagosomes.</span> <span class={"}journal_series_title{"}>Cell. Microbiol.</span>, <span class={"}journal_volume{"}>vol 8</span> <span class={"}journal_pages{"}>pp 690-703</span>.</div> <div class={"}article_info{"}>S Bauer, P L{\"o}nnbro, P Nordenfelt and H Tapper. <span class={"}article_issue_date{"}>2006</span>. <span class={"}article_title{"}>S. pyogenes bacteria survive in neutrophil-differentiated HL-60 cells by inhibiting the fusion of azurophilic granules with phagosomes.</span> (manuscript)</div> <div class={"}article_info{"}>S Bauer, M Abdgawad, L Gunnarsson, M Segelmark, H Tapper and T Hellmark. <span class={"}article_issue_date{"}>2006</span>. <span class={"}article_title{"}>Proteinase 3 and CD177 are expressed on the plasma membrane of the same subset of neutrophils.</span> <span class={"}journal_series_title{"}>J. Leukoc. Biol.</span>, (accepted)</div>",

year = "2006",

language = "English",

isbn = "91-85559-48-2",

series = "Lund University Faculty of Medicine Doctoral Dissertation Series ",

publisher = "Department of Clinical Sciences, Lund University",

school = "Infection Medicine (BMC)",

}

TY - THES

T1 - Membrane traffic in neutrophils and neutrophil-like cells

AU - Bauer, Susanne

N1 - Defence details Date: 2006-11-17 Time: 09:15 Place: Segerfalksalen, Biomedicinskt Centrum, Sölvegatan 19, Lund. External reviewer(s) Name: Lundqvist, Helen Title: [unknown] Affiliation: Medicinsk mikrobiologi, Molekylär och Klinisk Medicin (IMK), Linköpings Universitet --- <div class="article_info">S Bauer and H Tapper. <span class="article_issue_date">2004</span>. <span class="article_title">Membrane retrieval in neutrophils during phagocytosis: inhibition by M protein-expressing S. pyogenes bacteria.</span> <span class="journal_series_title">J. Leukoc. Biol.</span>, <span class="journal_volume">vol 76</span> <span class="journal_pages">pp 1142-1150</span>.</div> <div class="article_info">L Staali, S Bauer, M Mörgelin, L Björck and H Tapper. <span class="article_issue_date">2006</span>. <span class="article_title">Streptococcus pyogenes bacteria modulate membrane traffic in human neutrophils and selectively inhibit azurophilic granule fusion with phagosomes.</span> <span class="journal_series_title">Cell. Microbiol.</span>, <span class="journal_volume">vol 8</span> <span class="journal_pages">pp 690-703</span>.</div> <div class="article_info">S Bauer, P Lönnbro, P Nordenfelt and H Tapper. <span class="article_issue_date">2006</span>. <span class="article_title">S. pyogenes bacteria survive in neutrophil-differentiated HL-60 cells by inhibiting the fusion of azurophilic granules with phagosomes.</span> (manuscript)</div> <div class="article_info">S Bauer, M Abdgawad, L Gunnarsson, M Segelmark, H Tapper and T Hellmark. <span class="article_issue_date">2006</span>. <span class="article_title">Proteinase 3 and CD177 are expressed on the plasma membrane of the same subset of neutrophils.</span> <span class="journal_series_title">J. Leukoc. Biol.</span>, (accepted)</div>

PY - 2006

Y1 - 2006

N2 - 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.

AB - 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.

KW - Infections

KW - membrane traffic

KW - Hematologi

KW - extracellular fluids

KW - Haematology

KW - Medicin (människa och djur)

KW - Medicine (human and vertebrates)

KW - CD177

KW - extracellulära vätskor

KW - PR3

KW - phagocytosis

KW - Streptococcus pyogenes

KW - Infektioner

KW - neutrophils

M3 - Doctoral Thesis (compilation)

SN - 91-85559-48-2

T3 - Lund University Faculty of Medicine Doctoral Dissertation Series

PB - Department of Clinical Sciences, Lund University

ER -

Membrane traffic in neutrophils and neutrophil-like cells

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Bibliografisk information

Ämnesklassifikation (UKÄ)

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