Bactericidal/Permeability-Increasing Protein (BPI) and Proteinase 3: Studies at the Transcriptional Level

Katrien Pieters

Research output: ThesisDoctoral Thesis (compilation)

149 Downloads (Pure)

Abstract

In myelopoiesis, neutrophils and monocytes/macrophages are formed from a common myeloid precursor cell in the bone marow. During maturation of neutrophils, cytoplasmic granules are formed in the cells and the content of these granules is critical for the function of neutrophils in the first line of defense against invading microorganisms. The Bactericidal/Permeability-Increasing protein (BPI) is stored in azurophil granules of the neutrophil and is cytotoxic against gram-negative bacteria. Absence of BPI in neutrophils of patients with Specific Granule Deficiency (SGD) and late expression of BPI at the promyelocyte stage, suggest a different regulation at the transcriptional level as compared to other azurophil granule proteins. In this thesis, we show that the transcription factors AML-1, PU.1, and Sp3 regulate the expression of human BPI in myeloid cells. We also identified a mouse ortholog to human BPI, expressed in bone marrow, testis and epididymis. However, the expression of BPI in mouse bone marrow cells is much lower than that in human bone marrow cells, indicating important differences in the transcriptional regulation. We suggest that, in contrast to human BPI, lack of C/EBP binding sites is responsible for the low expression of BPI in mouse bone marrow cells.

The expression of another azurophil granule protein, human proteinase 3, is shown to be increased in myeloid cells of patients with Wegener's Granulomatosis (WG). This increased expression of proteinase 3 might be a risk factor for the development of the disease. We show that the overrepresented ?564 A/G SNP in WG patients, which introduces a new potential Sp1 transcription factor binding site, is not the reason for increased proteinase 3 expression in these patients.
Original languageEnglish
QualificationDoctor
Awarding Institution
  • Division of Hematology and Transfusion Medicine
Supervisors/Advisors
  • Gullberg, Urban, Supervisor
Award date2005 Jun 9
Publisher
Print ISBNs91-85439-58-4
Publication statusPublished - 2005

Bibliographical note

Defence details

Date: 2005-06-09
Time: 09:15
Place: Biomedical Center (BMC), Segerfalksalen, Sölvegatan 19, Lund

External reviewer(s)

Name: Hellman, Lars
Title: Professor
Affiliation: Institute of cell-and Molecular Biology, University of Uppsala

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<div class="article_info">Andreas Lennartsson, Katrien Pieters, Tove Ullmark, Karina Vidovic and Urban Gullberg. <span class="article_issue_date">2003</span>. <a href="javascript:downloadFile(545033)" class="article_link">AML-1, PU.1, and Sp3 regulate expression of human bactericidal/permeability-increasing protein</a> <span class="journal_series_title">Biochemical and Biophysical Research Communications</span>, <span class="journal_volume">vol 311</span> <span class="journal_pages">pp 853-863</span>. <span class="journal_distributor">Elsevier</span></div>
<div class="article_info">Andreas Lennartsson, Katrien Pieters, Karina Vidovic and Urban Gullberg. <span class="article_issue_date">2005</span>. <a href="javascript:downloadFile(545034)" class="article_link">A murine antibacterial ortholog to human bactericidal/permeability-increasing protein (BPI) is expressed in testis, epididymis, and bone marrow</a> <span class="journal_series_title">Journal of Leukocyte Biology</span>, <span class="journal_volume">vol 77</span> <span class="journal_pages">pp 369-377</span>. <span class="journal_distributor">Society for Leukocyte Biology</span></div>
<div class="article_info">Katrien Pieters, Andreas Lennartsson and Urban Gullberg. <span class="article_issue_date"></span>. <span class="article_title">Cloning and characterization of the mouse bactericidal/permeability-increasing protein (BPI) gene promoter</span> <span class="journal_pages">pp 13</span>. (manuscript)</div>
<div class="article_info">Katrien Pieters, Åsa Pettersson, Urban Gullberg and Thomas Hellmark. <span class="article_issue_date">2004</span>. <a href="javascript:downloadFile(545035)" class="article_link">The -564 A/G polymorphism in the promoter region of the proteinase 3 gene associated with Wegener's granulomatosis does not increase the promoter activity</a> <span class="journal_series_title">Clinical and Experimental Immunology</span>, <span class="journal_volume">vol 138</span> <span class="journal_pages">pp 266-270</span>. <span class="journal_distributor">Blackwell Publishing Ltd</span></div>

Subject classification (UKÄ)

  • Hematology

Keywords

  • azurophil granules
  • myelopoiesis
  • BPI
  • mouse ortholog
  • proteinase 3
  • transcriptional regulation
  • Wegener's Granulomatosis (WG)
  • SNP
  • Medicine (human and vertebrates)
  • extracellulära vätskor
  • Hematologi
  • extracellular fluids
  • Haematology
  • Medicin (människa och djur)

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