Contribution of myeloperoxidase to coronary artery vasculitis associated with MPO-ANCA production.
The role of myeloperoxidase (MPO) in the pathogenesis of vasculitis associated with MPO-specific anti-neutrophil cytoplasmic autoantibody (MPO-ANCA) was examined in a murine animal model. Coronary artery vasculitis was induced in C57BL/6 mice with and without endogenous MPO by intraperitoneal injection of Candida albicans-derived substances (CADS). The corresponding levels of MPO-ANCA in sera of mice with and without vasculitis were measured and compared in both wild-type and MPO-deficient animals. The MPO-ANCA titers in sera were significantly higher in mice with vasculitis than in vasculitis-negative mice, indicating that MPO-ANCA correlated with vasculitis formation. However, the increase of MPO-ANCA titers observed in sera of wild C57BL/6 mice were strongly suppressed in MPO-deficient C57BL/6 mice, accompanied with prevention of vasculitis formation. These results show that MPO acted as an antigen for MPO-ANCA production by CADS and was followed by the vasculitis formation. Vasculitis did develop in a few MPO-deficient mice, though the incidence of vasculitis was much lower in MPO-deficient mice than in C57BL/6 mice.
Ishida-Okawara
A
A
Department of Bioactive Molecules, National Institute of Infectious Diseases, Tokyo, Japan.
Oharaseki
T
T
Takahashi
K
K
Hashimoto
Y
Y
Aratani
Y
Y
Koyama
H
H
Maeda
N
N
Naoe
S
S
Suzuki
K
K
D000818:Animals; D019268:Antibodies, Antineutrophil Cytoplasmic / Q000097:blood / Q000276:immunology* / Q000502:physiology; D000974:Antibodies, Antinuclear / Q000097:blood; D000918:Antibody Specificity; D000946:Antigens, Fungal / Q000008:administration & dosage; D003324:Coronary Artery Disease / Q000201:enzymology / Q000209:etiology / Q000276:immunology; D004195:Disease Models, Animal; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009195:Peroxidase / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D014657:Vasculitis / Q000201:enzymology* / Q000209:etiology / Q000276:immunology*
D019268:Antibodies, Antineutrophil Cytoplasmic; D000974:Antibodies, Antinuclear; D000946:Antigens, Fungal; D009195:Peroxidase