Proteinase 3 and Neutrophil Apoptosis in ANCA-Associated Systemic Vasculitis

Research output: ThesisDoctoral Thesis (compilation)

Abstract

ANCA-Associated Systemic Vasculitis (AASV) is characterized by leukocytoclasis- dying neutrophils surrounding small blood vessels. Previous studies have shown increased plasma PR3 and increased proportion of neutrophils expressing plasma membrane-associated PR3 (mPR3+).
Neutrophils were isolated by polymorphprep and membrane expression was measured by FACS. Plasma PR3, pro-PR3 and cytokines were measured by ELISA. Neutrophil apoptosis was measured by FACS after 20h in vitro culture. Expression of pro/anti-apoptotic factors and transcription factors C/EBP-α, C/EBP-β and PU.1 was measured by real-time PCR.
Plasma PR3, pro-PR3, and proportion of mPR3+neutrophils were elevated in AASV. mPR3 and CD177 were co-expressed on a subset of neutrophils both in AASV and controls. mPR3 expression was not correlated directly to circulating PR3 or PR3 gene transcription, but was dependent on transcription of the CD177 gene. AASV neutrophils had a significantly lower rate of apoptosis than neutrophils from healthy blood donors (HBD). Lower apoptosis rate did not correlate with clinical data, plasma PR3, cytokine levels, mPR3 expression or level of pro/anti-apoptotic factors. However, C/EBP-α and C/EBP-β were significantly higher in neutrophils from AASV patients than in HBD neutrophils.
These results indicate an altered neutrophil phenotype in AASV and suggest that the rate of granulopoiesis is higher, while the rate of neutrophil apoptosis is lower. This may predispose for the presence of dying neutrophils in regions of inflammation in AASV. Additional studies are required to determine why the rate of neutrophil apoptosis is lower in AASV patients and if dysregulation of neutrophil apoptosis contributes directly to the pathogenesis.

Details

Authors
  • Mohamed AbdGawad
Organisations
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Urology and Nephrology

Keywords

  • Wegener’s granulomatosis, anti-neutrophil cytoplasmic antibody (ANCA). Proteinase 3 (PR3), myeloperoxidase (MPO). Flowcytometry (FACS). Vasculitis., microscopic polyangitis
Original languageEnglish
QualificationDoctor
Awarding Institution
Supervisors/Assistant supervisor
Award date2010 Oct 29
Publisher
  • Lund University
Print ISBNs978-91-86671-11-2
Publication statusPublished - 2010
Publication categoryResearch

Bibliographic note

Defence details Date: 2010-10-29 Time: 09:00 Place: Föreläsningssalen, Alwall huset, Barngatan 2, Lunds Universitetssjukhus External reviewer(s) Name: Kettritz, Ralph Title: Professor Affiliation: Professor ---

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Related research output

AbdGawad, M., Gunnarsson, L., Anders Bengtsson, Pierre Geborek, Nilsson, L., Mårten Segelmark & Thomas Hellmark, 2010, In : Clinical and Experimental Immunology. 161, p. 89-97

Research output: Contribution to journalArticle

Bauer, S., AbdGawad, M., Gunnarsson, L., Mårten Segelmark, Tapper, H. & Thomas Hellmark, 2007, In : Journal of Leukocyte Biology. 81, p. 458-464

Research output: Contribution to journalArticle

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