The role of neutrophils in the induction of glomerulonephritis by anti-myeloperoxidase antibodies

Am J Pathol. 2005 Jul;167(1):39-45. doi: 10.1016/S0002-9440(10)62951-3.


In humans, circulating anti-neutrophil cytoplasm autoantibodies (ANCAs) with specificity for myeloperoxidase (MPO) are strongly associated with the development of pauci-immune necrotizing and crescentic glomerulonephritis (NCGN). In mice, we have demonstrated that intravenous injection of mouse antibodies specific for mouse MPO induces NCGN that closely mimics the human disease. We now report that the development of NCGN in this experimental model is accompanied by glomerular accumulation of neutrophils and macrophages. Neutrophil infiltration was most conspicuous at sites of glomerular necrosis and crescent formation, with macrophages also most numerous in crescents. Lymphocytes, however, were sparse in acute lesions. Importantly, mice that were depleted of circulating neutrophils with NIMP-R14 rat monoclonal antibodies were completely protected from anti-MPO IgG-induced NCGN. These findings provide direct evidence that neutrophils play a major role in the pathogenesis of anti-MPO-induced NCGN in this animal model and implicate neutrophils in the induction of human ANCA disease. This raises the possibility that therapeutic strategies to reduce circulating neutrophils could be beneficial to patients with ANCA-induced NCGN.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antibodies, Antineutrophil Cytoplasmic / immunology*
  • Disease Models, Animal
  • Glomerulonephritis / immunology*
  • Glomerulonephritis / pathology
  • Macrophages / immunology
  • Mice
  • Neutrophil Activation / immunology
  • Neutrophils / immunology*
  • Peroxidase / immunology*


  • Antibodies, Antineutrophil Cytoplasmic
  • Peroxidase