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Phagocytosis of apoptotic cells by macrophages in anti-neutrophil cytoplasmic antibody-associated systemic vasculitis
Lund University, Sweden .
Lund University, Sweden .
Lund University, Sweden .
Lund University, Sweden .
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2012 (English)In: Clinical and Experimental Immunology, ISSN 0009-9104, E-ISSN 1365-2249, Vol. 170, no 1, 47-56 p.Article in journal (Refereed) Published
Abstract [en]

Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a group of autoimmune diseases, including granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA). It is not known why ANCA develop, but it has been shown that they participate in pathogenesis by activating polymorphonuclear neutrophils (PMNs). In this study we hypothesize that dysregulation of phagocytosis in AAV leads to the accumulation of apoptotic neutrophils seen in association with blood vessels in AAV. These cells progress into secondary necrosis, contributing to tissue damage and autoantibody formation. Peripheral blood cells were counted, and phagocytosis was investigated using monocyte-derived macrophages (M circle divide) and PMNs from healthy blood donors (HBD), AAV patients and systemic lupus erythematosus (SLE) patients. Furthermore, the effect of serum was assessed. Phagocytosis was measured using flow cytometry. The results showed no deviation in monocyte subpopulations for AAV patients compared to HBDs, although there was a decrease in lymphocyte and pDC (plasmacytoid dendritic cell) populations (4.2 X 106 cells/l versus 10.4 X 106 cells/l, P andlt; 0.001). The number of neutrophils was increased (6.0 X 109 cells/l versus 3.8 X 109 cells/l, P andlt; 0.001). There were no differences found in the ability of M circle divide s to engulf apoptotic cells, nor when comparing apoptotic PMNs to become engulfed. However, serum from AAV donors tended to decrease the phagocytosis ability of M circle divide s (36%) compared to serum from HBDs (43%). In conclusion, there is no intrinsic dysfunction in the M circle divide s or in the PMNs that have an effect on phagocytic activity, but ANCA may play a role by decreasing phagocytic ability.

Place, publisher, year, edition, pages
Wiley-Blackwell , 2012. Vol. 170, no 1, 47-56 p.
Keyword [en]
ANCA-associated vasculitis (AAV), autoimmunity, monocyte subpopulations, neutrophil, pDC
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:liu:diva-82040DOI: 10.1111/j.1365-2249.2012.04633.xISI: 000308289500006OAI: oai:DiVA.org:liu-82040DiVA: diva2:558026
Note

Funding Agencies|Crafoord foundation||Thure Carlssons Minnesfond||Birgit o Sven Hakan Ohlssons foundation||Swedish Research Council|65x-15152|

Available from: 2012-10-01 Created: 2012-09-28 Last updated: 2017-12-07

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Segelmark, Mårten

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