Proteinase 3 and Neutrophil Apoptosis in ANCA-Associated Systemic Vasculitis

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.

Grantor dc:publisher

Lund University

Year dc:date

2010

Author dc:creator

• AbdGawad, Mohamed

• Clinical Medicine
• Wegener’s granulomatosis
• anti-neutrophil cytoplasmic antibody (ANCA). Proteinase 3 (PR3)
• myeloperoxidase (MPO). Flowcytometry (FACS). Vasculitis.
• microscopic polyangitis

Statement dc:rights

• info:eu-repo/semantics/openAccess

Language dc:language

eng

Identifier

urn:isbn:978-91-86671-11-2

OAI identifier oai:identifier

oai:lup.lub.lu.se:df1ca3fd-b33c-4462-a170-97eee9bad915