Xu Peng-cheng, Li Zhi-ying, Yang Xiao-wei, Zhao Ming-hui, Chen Min
1Renal Division, Department of Medicine, Peking University First Hospital, Institute of Nephrology, Peking University, Key Laboratory of Renal Disease, Ministry of Health of China, Peking-Tsinghua Center for Life Sciences, Beijing, PR China.
Innate Immun. 2014 May;20(4):440-8. doi: 10.1177/1753425913508164. Epub 2013 Nov 4.
In patients with active anti-neutrophil cytoplasmic Ab (ANCA)-associated vasculitis (AAV), there are high levels of circulating C-reactive protein (CRP), which can inhibit the alternative complement pathway by binding factor H and triggering the classical complement pathway by binding C1q. However, the alternative, not the classical, complement pathway has been proven to play an important role in AAV. We found that both purified myeloperoxidase (MPO) and MPO released from ANCA-stimulated neutrophils could bind modified CRP (mCRP), but not pentameric CRP. Furthermore, MPO could block the binding between mCRP and factor H, as well as the binding between mCRP and C1q. Binding with mCRP did not influence the enzymatic activity of MPO. Binding with mCRP also did not influence the binding between MPO and its physical inhibitor, ceruloplasmin, as well as the binding between MPO and MPO-ANCA. The results indicated that MPO might be a complement regulator and inhibit the negative regulatory effect of CRP on the alternative complement pathway.
在患有活动性抗中性粒细胞胞浆抗体（ANCA）相关性血管炎（AAV）的患者中，循环中的C反应蛋白（CRP）水平很高，CRP可通过结合因子H抑制替代补体途径，并通过结合C1q触发经典补体途径。然而，已证实替代补体途径而非经典补体途径在AAV中起重要作用。我们发现，纯化的髓过氧化物酶（MPO）和从ANCA刺激的中性粒细胞释放的MPO都能结合修饰的CRP（mCRP），但不能结合五聚体CRP。此外，MPO可阻断mCRP与因子H之间的结合，以及mCRP与C1q之间的结合。与mCRP结合不会影响MPO的酶活性。与mCRP结合也不会影响MPO与其物理抑制剂铜蓝蛋白之间的结合，以及MPO与MPO-ANCA之间的结合。结果表明，MPO可能是一种补体调节剂，并抑制CRP对替代补体途径的负调节作用。
