Phagocytosis of apoptotic cells by macrophages in anti-neutrophil cytoplasmic antibody-associated systemic vasculitis.
(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:
https://lup.lub.lu.se/record/3124408
- author
- Ohlsson, Susanne LU ; Pettersson, Åsa LU ; Ohlsson, Sophie LU ; Selga, Daina LU ; Bengtsson, A A ; Segelmark, Mårten LU and Hellmark, Thomas LU
- organization
- publishing date
- 2012
- 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
- pmid:22943200
- 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
- 2016-04-04 08:53:53
- date last changed
- 2022-02-20 22:23:18
@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 < 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.}}, 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}}, doi = {{10.1111/j.1365-2249.2012.04633.x}}, volume = {{170}}, year = {{2012}}, }