| Project/Area Number |
12670222
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Experimental pathology
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| Research Institution | National Institute of Infections Diseases |
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Principal Investigator |
SUZUKI Kazuo Dept. of Bioactive Molecules, National Institute of Infections Diseases, Chief of Laboratory, 生物活性物質部, 研究員 (20192130)
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| Co-Investigator(Kenkyū-buntansha) |
ARATANI Yasuaki Kihara Biological Institute, Associate prof. Yokohama City University., 木原生物学研究所, 助教授 (30192470)
TAKAHASHI Kei Dept. of Pathology, Associate prof. Toho University, School of Medicine, Ohashi Hospital, 医学部, 助教授 (80216712)
OKAWARA Akiko Dept. of Bioactive Molecules, National Institute of Infections Diseases, Research Associate, 生物活性物質部, 研究員 (30260277)
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| Project Period (FY) |
2000 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2001: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 2000: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Keywords | MYELOPEROXIDASE(MPO) / MPO DEFICIENT MOUSE / NEUTROPHILS / ANTI-NEUTROPHIL ANTIBODY MPO-ANCA / VASCULITIS / CRESENTIC GLOERULONEPHIRITIS / POLYMORPHISM OF GENES / SCG / KJ MOUSE / Myeloperoxidase / MPO欠損遺伝子 / MPO-ANCA / Candida albicans / リコンビナント mMPO / 血管炎発症 / 自己抗体 |
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| Research Abstract |
The role of myeloperoxidase (MPO) for vasculitis formation accompanied with the production of MPO-specific anti-neutrophil cytoplasmic autoantibody (MPO-ANCA) was analyzed using wild and MPO-deficient mice. MPO-ANCA levels in sera of wild type. C57BL/6 mice with vasculitis particularly in the coronary arteries induced by injection of Candida albicans-derived substances (CADS) increased. 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. In addition, the role of activated neutrophils in the development of nephritis was investigated by evaluating the relationship between neutrophil functions and renal lesion of SCG/Kj mice that spontaneously develop crescentic glomerulonephritis from a young age. Functions of activated neutrophils were evaluated by measuring MPO release and superoxide generation from peripheral neutrophils. Serum levels of MPO-ANCA, a potent marker of active vasculitis, were also measured. In the early phase of nephritis, spontaneous release of MPO from peripheral neutrophils of SCG/Kj mice significantly increased. Numbers of neutrophils both in peripheral blood and infiltrated into glomeruli gradually increased along with the development of nephritis.
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