Guilpain Philippe, Servettaz Amélie, Batteux Frédéric, Guillevin Loïc, Mouthon Luc
Paris Descartes University, Faculty of Medicine, UPRES EA 4058, Department of Internal Medicine, Paris, France.
Autoimmun Rev. 2008 Jun;7(6):421-5. doi: 10.1016/j.autrev.2008.03.009. Epub 2008 Apr 10.
Myeloperoxidase (MPO) is a cationic protein present in primary azurophilic granules of neutrophils and monocytes. MPO produces a highly deleterious reactive oxygen species, the hypochlorous acid (HOCl), using hydrogen peroxide (H(2)O(2)) and chloride ions as substrate. Anti-MPO antibodies (Abs) are present in 70% of the cases in patients with microscopic polyangiitis (MPA), a small-sized vessel vasculitis. Anti-MPO Abs from patients with MPA can trigger the release of MPO by neutrophils and monocytes. Anti-MPO Abs can activate MPO to generate an oxidative stress deleterious for the endothelium. Thus, we recently demonstrated that MPA sera with anti-MPO Abs activated MPO in vitro, and generated hypochlorous acid, whereas sera from MPA patients with no anti-MPO Abs or healthy individuals did not. Both hypochlorous acid production and endothelial lysis were abrogated by N-acetylcysteine (NAC), an antioxidant molecule. Thus, anti-MPO Abs could play a pathogenic role in vivo by triggering an oxidative burst leading to severe endothelial damages.
髓过氧化物酶（MPO）是一种存在于中性粒细胞和单核细胞的初级嗜天青颗粒中的阳离子蛋白。MPO利用过氧化氢（H₂O₂）和氯离子作为底物产生一种极具危害性的活性氧——次氯酸（HOCl）。抗MPO抗体（Abs）存在于显微镜下多血管炎（MPA，一种小血管血管炎）患者70%的病例中。MPA患者的抗MPO抗体可触发中性粒细胞和单核细胞释放MPO。抗MPO抗体可激活MPO以产生对内皮细胞有害的氧化应激。因此，我们最近证明，含有抗MPO抗体的MPA血清在体外可激活MPO并产生次氯酸，而不含抗MPO抗体的MPA患者血清或健康个体的血清则不会。抗氧化分子N - 乙酰半胱氨酸（NAC）可消除次氯酸的产生和内皮细胞溶解。因此，抗MPO抗体可能通过引发氧化爆发导致严重的内皮损伤而在体内发挥致病作用。
