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Sökning: onr:"swepub:oai:DiVA.org:liu-77735" > Decreased Neutrophi...

Decreased Neutrophil Apoptosis in Quiescent ANCA-Associated Systemic Vasculitis

Abdgawad, Mohamed, (författare)
Lund University
Pettersson, Asa, (författare)
Lund University
Gunnarsson, Lena, (författare)
Lund University
visa fler...
Bengtsson, Anders A, (författare)
Lund University
Geborek, Pierre, (författare)
Lund University
Nilsson, Lars, (författare)
Lund University
Segelmark, Mårten, (författare)
Linköpings universitet, Farmakologi, Linköpings universitet, Hälsouniversitetet, Östergötlands Läns Landsting, Njurmedicinska kliniken US
Hellmark, Thomas, (författare)
Lund University
visa färre...
2012
Engelska.
Ingår i: PLoS ONE. - Public Library of Science. - 1932-6203 .- 1932-6203. ; 7:3
  • Tidskriftsartikel (refereegranskat)
Abstract Ämnesord
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  • <p>Background: ANCA-Associated Systemic Vasculitis (AASV) is characterized by leukocytoclasis, accumulation of unscavenged apoptotic and necrotic neutrophils in perivascular tissues. Dysregulation of neutrophil cell death may contribute directly to the pathogenesis of AASV. less thanbrgreater than less thanbrgreater thanMethods: Neutrophils from Healthy Blood Donors (HBD), patients with AASV most in complete remission, Polycythemia Vera (PV), Systemic Lupus Erythematosus (SLE), Rheumatoid Arthritis (RA) and renal transplant recipients (TP) were incubated in vitro, and the rate of spontaneous apoptosis was measured by FACS. Plasma levels of cytokines and sFAS were measured with cytometric bead array and ELISA. Expression of pro/anti-apoptotic factors, transcription factors C/EBP-alpha, C/EBP-beta and PU.1 and inhibitors of survival/JAK2-pathway were measured by real-time-PCR. less thanbrgreater than less thanbrgreater thanResults: AASV, PV and RA neutrophils had a significantly lower rate of apoptosis compared to HBD neutrophils (AASV 50 +/- 14% vs. HBD 64 +/- 11%, p andlt; 0.0001). In RA but not in AASV and PV, low apoptosis rate correlated with increased plasma levels of GM-CSF and high mRNA levels of anti-apoptotic factors Bcl-2A1 and Mcl-1. AASV patients had normal levels of G-CSF, GM-CSF and IL-3. Both C/EBP-alpha, C/EBP-beta were significantly higher in neutrophils from AASV patients than HBD. Levels of sFAS were significantly higher in AASV compared to HBD. less thanbrgreater than less thanbrgreater thanConclusion: Neutrophil apoptosis rates in vitro are decreased in AASV, RA and PV but mechanisms seem to differ. Increased mRNA levels of granulopoiesis-associated transcription factors and increased levels of sFAS in plasma were observed in AASV. Additional studies are required to define the mechanisms behind the decreased apoptosis rates, and possible connections with accumulation of dying neutrophils in regions of vascular lesions in AASV patients.</p>

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  (hsv//swe)
MEDICAL AND HEALTH SCIENCES  (hsv//eng)

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MEDICINE
MEDICIN

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