The role of neutrophils in the induction of glomerulonephritis by anti-myeloperoxidase antibodies.
Am J Pathol
; 167(1): 39-45, 2005 Jul.
Article
em En
| MEDLINE
| ID: mdl-15972950
ABSTRACT
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.
Texto completo:
1
Coleções:
01-internacional
Temas:
Geral
Base de dados:
MEDLINE
Assunto principal:
Peroxidase
/
Anticorpos Anticitoplasma de Neutrófilos
/
Glomerulonefrite
/
Neutrófilos
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Am J Pathol
Ano de publicação:
2005
Tipo de documento:
Article
País de afiliação:
Estados Unidos