Neutrophil dysfunction induced by hyperglycemia: modulation of myeloperoxidase activity
Neutrophil dysfunction induced by hyperglycemia: modulation of myeloperoxidase activity
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DOI：
10.1002/cbf.2840
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发表时间：
2012-10-01
影响因子：
3.6
通讯作者：
Rodrigues, Maria Rita
中科院分区：
文献类型：
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作者：
Ferreira, Claudia de Souza;Araujo, Tomaz Henrique;Rodrigues, Maria Rita
我们的数据表明，髓过氧化物酶（MPO）活性受损可能在高血糖大鼠中性粒细胞功能障碍中发挥重要作用。中性粒细胞生化途径包括 NADPH 氧化酶系统和 MPO 酶。它们都在中性粒细胞的杀伤功能中发挥重要作用。本文评估高血糖对这些酶活性的影响以及对白色念珠菌吞噬作用和大鼠腹膜中性粒细胞的杀菌特性的影响。使用化学发光和细胞色素 C 还原测定法测量 NADPH 氧化酶系统活性。通过监测 HOCl 的产生来测量 MPO 活性，并使用蛋白质印迹和免疫荧光分析 MPO 蛋白表达。使用 MayGrunwaldGiemsa 染色方法通过光学显微镜评估白色念珠菌的吞噬作用和死亡。糖尿病组的 ROS 生成动力学略有延迟。糖尿病中性粒细胞中 MPO 表达水平较高；然而，与对照组相比，这些中性粒细胞中的 MPO 活性有所降低。糖尿病中性粒细胞中白色念珠菌的吞噬和杀灭作用较低。根据我们的实验模型，由于 HOCl 产生减少，糖尿病大鼠中性粒细胞吞噬和杀伤功能受损，凸显了 MPO 在中性粒细胞杀菌功能中的重要性。版权所有 (c) 2012 John Wiley & Sons, Ltd.
Our data suggest that impaired activity of myeloperoxidase (MPO) may play an important role in the dysfunction of neutrophils from hyperglycemic rats. Neutrophil biochemical pathways include the NADPH oxidase system and the MPO enzyme. They both play important role in the killing function of neutrophils. The effect of hyperglycemia on the activity of these enzymes and the consequences with regard to Candida albicans phagocytosis and the microbicidal property of rat peritoneal neutrophils is evaluated here. The NADPH oxidase system activity was measured using chemiluminescence and cytochrome C reduction assays. MPO activity was measured by monitoring HOCl production, and MPO protein expression was analysed using Western blot and immunofluorescence. C. albicans phagocytosis and death were evaluated by optical microscopy using the MayGrunwaldGiemsa staining method. ROS generation kinetic was slightly delayed in the diabetic group. MPO expression levels were higher in diabetic neutrophils; however, MPO activity was decreased in these same neutrophils compared with the controls. C. albicans phagocytosis and killing were lower in the diabetic neutrophils. Based on our experimental model, the phagocytic and killing functions of neutrophil phagocytosis are impaired in diabetic rats because of the decreased production of HOCl, highlighting the importance of MPO in the microbicidal function of neutrophils. Copyright (c) 2012 John Wiley & Sons, Ltd.