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

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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.

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Subject classification (UKÄ) – MANDATORY

  • Immunology in the medical area
Original languageEnglish
Pages (from-to)47-56
JournalClinical and Experimental Immunology
Volume170
Issue number1
Publication statusPublished - 2012
Publication categoryResearch
Peer-reviewedYes

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