A novel mouse model for MPO-ANCA-associated glomerulonephritis.
We established a novel model mouse for myeloperoxidase anti-neutrophil cytoplasmic antibody (MPO-ANCA)-associated glomerulonephritis with crescentic formation, which was induced by administering bovine serum albumin (BSA). Neutrophil infiltration into the renal glomeruli began at 8 weeks and crescent formation was observed from 10 weeks after the first BSA injection. Platelet and neutrophil counts significantly increased, and proteinuria was observed from 5 weeks. MPO-ANCA increased slightly at 4 and markedly at 9 weeks, and the TNF-alpha level increased at 11 weeks. Glomerular neutrophil infiltration was correlated with MPO-ANCA levels. In addition, proteinuria also significantly correlated with MPO-ANCA levels. Finally, renal crescent formation was associated with an increase of MPO-ANCA levels and neutrophil infiltration into glomeruli. The glomerular immune deposition of IgG and C3 was observed. These findings indicate that BSA induces neutrophil activation of peripheral blood followed by the elevation of MPO-ANCA, resulting in the development of crescentic glomerulonephritis in mice.
Department of Medicine, Kidney Center, Tokyo Women's Medical University, Japan. yumura@kc.twmu.ac.jp
Wako
W
Yumura
Mitsuyo
M
Itabashi
Akiko
A
Ishida-Okawara
Kazuo
K
Tomizawa
Junji
J
Yamashita
Yoshiaki
Y
Kaneshiro
Hiroshi
H
Nihei
Kazuo
K
Suzuki
D000818:Animals; D019268:Antibodies, Antineutrophil Cytoplasmic / Q000097:blood / Q000276:immunology*; D001806:Blood Urea Nitrogen; D003404:Creatinine / Q000097:blood; D004195:Disease Models, Animal; D005260:Female; D005434:Flow Cytometry; D005921:Glomerulonephritis / Q000201:enzymology* / Q000276:immunology* / Q000473:pathology; D007150:Immunohistochemistry; D007958:Leukocyte Count; D008168:Lung / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D009195:Peroxidase / Q000097:blood / Q000276:immunology*; D010976:Platelet Count; D011507:Proteinuria; D012710:Serum Albumin, Bovine / Q000276:immunology; D013047:Specific Pathogen-Free Organisms; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
D019268:Antibodies, Antineutrophil Cytoplasmic; D014409:Tumor Necrosis Factor-alpha; D012710:Serum Albumin, Bovine; D003404:Creatinine; D009195:Peroxidase