Membrane traffic in neutrophils and neutrophil-like cells

Susanne Bauer

Research output: ThesisDoctoral Thesis (compilation)

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.
Original languageEnglish
QualificationDoctor
Awarding Institution
  • Infection Medicine (BMC)
Supervisors/Advisors
  • Tapper, Hans, Supervisor
  • Björck, Lars, Supervisor
Award date2006 Nov 17
Publisher
Print ISBNs91-85559-48-2
Publication statusPublished - 2006

Bibliographical note

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

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<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>

Subject classification (UKÄ)

  • Infectious Medicine

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

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