Opsonization of apoptotic neutrophils by anti-neutrophil cytoplasmic antibodies (ANCA) leads to enhanced uptake by macrophages and increased release of tumour necrosis factor-alpha (TNF-alpha)

Clin Exp Immunol. 2000 Dec;122(3):499-503. doi: 10.1046/j.1365-2249.2000.01410.x.


Since proteinase 3 (PR3)-ANCA interact with PR3 on the surface of apoptotic polymorphonuclear neutrophils (PMN) and ingestion of apoptotic PMN is known to modulate macrophage inflammatory reactions, we raised the question whether PR3-ANCA-opsonized apoptotic PMN influence the uptake by macrophages and their state of activation. We therefore analysed the effects of PR3-ANCA-opsonized apoptotic PMN on the uptake process by enzymatic assay. We further investigated the production of TNF-alpha, IL-10, IL-12 and the secretion of lipid inflammatory mediators (TxB2, leukotriene B4 (LTB4) and prostaglandin E2 (PGE2)) by human monocyte-derived macrophages using FACS and ELISA methods. We show that PMN-opsonization by PR3-ANCA substantially enhances phagocytosis by macrophages and thereby triggers the production of TNF-alpha and TxB2. These in vitro findings indicate that PR3-ANCA opsonization of apoptotic PMN might be an important mechanism in the pathogenesis of Wegener's granulomatosis (WG), prompting macrophages to produce proinflammatory mediators. These mediators, mainly TNF-alpha, might prime further PMN leading to perpetuation of the known priming-dependent mechanisms of ANCA action.

MeSH terms

  • Antibodies, Antineutrophil Cytoplasmic / immunology*
  • Apoptosis / immunology*
  • Dinoprostone / metabolism
  • Granulomatosis with Polyangiitis / blood
  • Granulomatosis with Polyangiitis / immunology*
  • Humans
  • Interleukin-10 / biosynthesis
  • Interleukin-12 / biosynthesis
  • Leukotriene B4 / metabolism
  • Macrophages / immunology*
  • Macrophages / metabolism
  • Myeloblastin
  • Neutrophils / immunology*
  • Opsonin Proteins / immunology*
  • Phagocytosis / immunology*
  • Serine Endopeptidases / immunology*
  • Thromboxane B2 / metabolism
  • Tumor Necrosis Factor-alpha / biosynthesis*


  • Antibodies, Antineutrophil Cytoplasmic
  • Opsonin Proteins
  • Tumor Necrosis Factor-alpha
  • Interleukin-10
  • Interleukin-12
  • Leukotriene B4
  • Thromboxane B2
  • Serine Endopeptidases
  • Myeloblastin
  • Dinoprostone