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Phagocytosis of apoptotic cells by macrophages in anti-neutrophil cytoplasmic antibody-associated systemic vasculitis.

Ohlsson, Susanne LU ; Pettersson, Åsa LU ; Ohlsson, Sophie LU ; Selga, Daina LU ; Bengtsson, A A; Segelmark, Mårten LU and Hellmark, Thomas LU (2012) In Clinical and Experimental Immunology 170(1). p.47-56
Abstract
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 (MØ) and PMNs from healthy blood... (More)
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 (MØ) 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 × 10(6) cells/l versus 10·4 × 10(6) cells/l, P < 0·001). The number of neutrophils was increased (6·0 × 10(9) cells/l versus 3·8 × 10(9) cells/l, P < 0·001). There were no differences found in the ability of MØs to engulf apoptotic cells, nor when comparing apoptotic PMNs to become engulfed. However, serum from AAV donors tended to decrease the phagocytosis ability of MØs (36%) compared to serum from HBDs (43%). In conclusion, there is no intrinsic dysfunction in the MØs or in the PMNs that have an effect on phagocytic activity, but ANCA may play a role by decreasing phagocytic ability. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Clinical and Experimental Immunology
volume
170
issue
1
pages
47 - 56
publisher
British Society for Immunology
external identifiers
  • wos:000308289500006
  • pmid:22943200
  • scopus:84865652654
ISSN
0009-9104
DOI
10.1111/j.1365-2249.2012.04633.x
language
English
LU publication?
yes
id
5cb4c0ed-6b4d-46f2-a3fa-9a49c2a7971e (old id 3124408)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/22943200?dopt=Abstract
date added to LUP
2012-10-03 13:48:54
date last changed
2017-01-01 07:39:27
@article{5cb4c0ed-6b4d-46f2-a3fa-9a49c2a7971e,
  abstract     = {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 (MØ) 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 × 10(6) cells/l versus 10·4 × 10(6) cells/l, P &lt; 0·001). The number of neutrophils was increased (6·0 × 10(9) cells/l versus 3·8 × 10(9) cells/l, P &lt; 0·001). There were no differences found in the ability of MØs to engulf apoptotic cells, nor when comparing apoptotic PMNs to become engulfed. However, serum from AAV donors tended to decrease the phagocytosis ability of MØs (36%) compared to serum from HBDs (43%). In conclusion, there is no intrinsic dysfunction in the MØs or in the PMNs that have an effect on phagocytic activity, but ANCA may play a role by decreasing phagocytic ability.},
  author       = {Ohlsson, Susanne and Pettersson, Åsa and Ohlsson, Sophie and Selga, Daina and Bengtsson, A A and Segelmark, Mårten and Hellmark, Thomas},
  issn         = {0009-9104},
  language     = {eng},
  number       = {1},
  pages        = {47--56},
  publisher    = {British Society for Immunology},
  series       = {Clinical and Experimental Immunology},
  title        = {Phagocytosis of apoptotic cells by macrophages in anti-neutrophil cytoplasmic antibody-associated systemic vasculitis.},
  url          = {http://dx.doi.org/10.1111/j.1365-2249.2012.04633.x},
  volume       = {170},
  year         = {2012},
}