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

利用野生型和缺陷型小鼠，分析髓过氧化物酶(MPO)在血管炎形成和产生MPO特异性抗中性粒细胞胞浆抗体(MPO-ANCA)中的作用。野生型血清中MPO-ANCA水平。C57BL/6小鼠注射白色念珠菌衍生物质(CADS)诱发的脉管炎尤其是冠状动脉炎症加重。然而，野生型C57BL/6小鼠血清中MPO-ANCA滴度的升高在MPO缺陷型C57BL/6小鼠中受到强烈抑制，同时还能防止血管炎的形成。此外，通过评价自幼自发发展为新月体肾炎的SCG/KJ小鼠中性粒细胞功能与肾脏损害的关系，探讨了中性粒细胞在肾炎发生发展中的作用。通过检测外周血中中性粒细胞释放MPO和产生超氧化物来评价激活的中性粒细胞的功能。还检测了血清MPO-ANCA水平，MPO-ANCA是活动性血管炎的有效标志物。在肾炎早期，SCG/KJ小鼠外周血中性粒细胞自发释放MPO显著增加。随着肾炎的发展，外周血中的中性粒细胞和肾小球内的中性粒细胞逐渐增多。

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.