Department of Cellular Microbiology, Max Planck Institute for Infection Biology, Berlin, Germany.
Blood. 2011 Jan 20;117(3):953-9. doi: 10.1182/blood-2010-06-290171. Epub 2010 Oct 25.
The granule enzyme myeloperoxidase (MPO) plays an important role in neutrophil antimicrobial responses. However, the severity of immunodeficiency in patients carrying mutations in MPO is variable. Serious microbial infections, especially with Candida species, have been observed in a subset of completely MPO-deficient patients. Here we show that neutrophils from donors who are completely deficient in MPO fail to form neutrophil extracellular traps (NETs), indicating that MPO is required for NET formation. In contrast, neutrophils from partially MPO-deficient donors make NETs, and pharmacological inhibition of MPO only delays and reduces NET formation. Extracellular products of MPO do not rescue NET formation, suggesting that MPO acts cell-autonomously. Finally, NET-dependent inhibition of Candida albicans growth is compromised in MPO-deficient neutrophils. The inability to form NETs may contribute in part to the host defense defects observed in completely MPO-deficient individuals.
颗粒酶髓过氧化物酶（MPO）在中性粒细胞的抗菌反应中起着重要作用。然而，携带 MPO 突变的患者的免疫缺陷严重程度是可变的。在一组完全缺乏 MPO 的患者中观察到严重的微生物感染，特别是念珠菌属。在这里，我们表明，完全缺乏 MPO 的供体的中性粒细胞不能形成中性粒细胞胞外诱捕网（NETs），这表明 MPO 是 NET 形成所必需的。相比之下，部分 MPO 缺乏的供体的中性粒细胞形成 NETs，并且 MPO 的药理学抑制仅延迟和减少 NET 的形成。MPO 的细胞外产物不能挽救 NET 的形成，表明 MPO 具有自主作用。最后，MPO 缺陷中性粒细胞中的 NET 依赖性抑制白色念珠菌生长受损。不能形成 NETs 可能部分导致完全缺乏 MPO 的个体中观察到的宿主防御缺陷。
