Falk R J, Terrell R S, Charles L A, Jennette J C
Department of Medicine, University of North Carolina School of Medicine, Chapel Hill 27599.
Proc Natl Acad Sci U S A. 1990 Jun;87(11):4115-9. doi: 10.1073/pnas.87.11.4115.
Anti-neutrophil cytoplasmic autoantibodies (ANCA) are in the circulation of most patients with pauci-immune necrotizing vasculitis and pauci-immune crescentic glomerulonephritis. The current study demonstrates an effect of these autoantibodies on neutrophil function in vitro. ANCA cause normal human neutrophils to undergo an oxidative burst and degranulate. Both ANCA phenotypes (i.e., cytoplasmic-pattern ANCA and myeloperoxidase-specific ANCA) induce neutrophil activation. ANCA sera and purified immunoglobulins significantly increase the release of reactive oxygen species when compared with controls. ANCA, in a dose-dependent manner, induce the release of primary granule contents. These effects are markedly enhanced by priming neutrophils with tumor necrosis factor. Flow cytometry studies demonstrate the presence of myeloperoxidase on the surface of neutrophils after cytokine priming, indicating that primed neutrophils have ANCA antigens at their surfaces to interact with ANCA. These observations suggest an in vivo pathogenetic role for ANCA. We propose that, in patients with necrotizing vasculitis, ANCA-induced release of toxic oxygen radicals and noxious granule enzymes from cytokine-primed neutrophils could be mediating vascular inflammation.
抗中性粒细胞胞浆自身抗体（ANCA）存在于大多数寡免疫性坏死性血管炎和寡免疫性新月体性肾小球肾炎患者的血液循环中。目前的研究证明了这些自身抗体在体外对中性粒细胞功能的影响。ANCA可使正常人中性粒细胞发生氧化爆发并脱颗粒。两种ANCA表型（即胞浆型ANCA和髓过氧化物酶特异性ANCA）均可诱导中性粒细胞活化。与对照组相比，ANCA血清和纯化的免疫球蛋白可显著增加活性氧的释放。ANCA以剂量依赖的方式诱导初级颗粒内容物的释放。用肿瘤坏死因子预处理中性粒细胞可显著增强这些效应。流式细胞术研究表明，细胞因子预处理后中性粒细胞表面存在髓过氧化物酶，这表明预处理后的中性粒细胞表面具有ANCA抗原，可与ANCA相互作用。这些观察结果提示ANCA在体内具有致病作用。我们认为，在坏死性血管炎患者中，ANCA诱导细胞因子预处理的中性粒细胞释放有毒的氧自由基和有害的颗粒酶可能介导血管炎症。
