ANALYSIS OF DEVELOPMENT OF MPO-ANCA-RELATED VASCULITIS USING MPO DEFICIENCY

利用 MPO 缺乏分析 MPO-ANCA 相关血管炎的发展

基本信息

批准号：
12670222
负责人：
SUZUKI Kazuo
金额：
$ 2.18万
依托单位：
National Institute of Infections Diseases
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2000
资助国家：
日本
起止时间：
2000 至 2001
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12670222/
关键词：
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

项目摘要

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.

使用野生和MPO缺乏小鼠分析了脊髓过氧化物酶（MPO）在产生MPO特异性抗中性胞质自身抗体（MPO-ANCA）的作用。野生型血清中的mpo-anca水平。 C57BL/6小鼠患有血管炎，尤其是在注射白色念珠菌衍生物质（CADS）诱导的冠状动脉中增加的C57BL/6小鼠。但是，在缺乏MPO的C57BL/6小鼠中，在野生C57BL/6小鼠血清中观察到的MPO-ANCA滴度的增加，并伴有预防血管炎的形成。此外，通过评估中性粒细胞功能与SCG/KJ小鼠的肾脏病变之间的关系，研究了激活的中性粒细胞在肾炎发展中的作用，这些嗜中性粒细胞功能与肾脏病变之间的关系自发地从小就会自发发展新月形肾小球肾炎。通过测量从周围嗜中性粒细胞中的MPO释放和超氧化物产生来评估激活的中性粒细胞的功能。还测量了MPO-ANCA的血清水平是活性血管炎的有效标记。在肾炎的早期，从SCG/KJ小鼠的周围嗜中性粒细胞自发释放了MPO。周围血液中的中性粒细胞的数量随着肾炎的发展而逐渐增加。