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

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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.