The role of phagocytes in HIV-related oxidative stress
The role of phagocytes in HIV-related oxidative stress
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DOI：
10.1016/s1386-6532(00)00133-5
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发表时间：
2001-02-01
影响因子：
8.8
通讯作者：
Gougerot-Pocidalo, MA
中科院分区：
文献类型：
--
作者：
Elbim, C;Pillet, S;Gougerot-Pocidalo, MA
工作背景：吞噬细胞对各种刺激作出反应，释放大量活性氧（ROS），这是杀死细菌所必需的。然而，过量的ROS产生没有得到适当的抗氧化分子的补偿，可导致氧化应激，这也可能在HIV感染的发病机制中发挥重要作用。事实上，ROS参与慢性炎症、HIV复制和免疫系统细胞的凋亡。目的和研究设计：我们使用流式细胞术研究了在疾病的不同阶段，全血中多形核中性粒细胞（PMN）和单核细胞的活化和氧化还原状态。结果：我们发现，HIV感染患者的中性粒细胞和单核细胞自发产生的过氧化氢量增加。这种增加的H2 O2产生与细胞表面粘附分子表达的改变有关，这也反映了HIV感染患者吞噬细胞的基础活化。在单核细胞中，基础H2 O2产生与病毒载量相关。这种增加的ROS产生与抗凋亡/抗氧化化合物Bcl-2和硫氧还蛋白沿着疾病过程中的表达变化有关。这种调节可能是由氧化应激的双重调节引起的，至少可以部分解释为什么单核细胞数量在整个疾病过程中保持相对稳定。单核细胞表达正常的最大能力，产生活性氧在最佳条件下的刺激。相反，在用TNF α或IL-8离体引发后，嗜中性粒细胞显示响应于细菌N-甲酰肽的H2 O2产生减少。后一种损害与CD 4+淋巴细胞数量减少以及IL-8和IL-6血浆水平相关。结论：吞噬细胞增加的基础ROS产生可能参与了氧化损伤，这与HIV感染的病理生理学有关。此外，中性粒细胞引发H2 O2产生的减少可能导致HIV感染患者对细菌感染的易感性增加。(C)2001 Elsevier Science B. V.保留所有权利。
Background: in response to a variety of stimuli, phagocytes release large quantities of reactive oxygen species (ROS), which are essential for bacterial killing. However, excessive ROS production not appropriately compensated by antioxidant molecules can lead to oxidative stress, which may also play an important role in pathogenesis of HIV infection. In fact, ROS participate in chronic inflammation, HIV replication and the apoptosis of cells of the immune system. Objective and study design: we used flow cytometry to study, in whole blood, the activation and redox status of polymorphonuclear neutrophils (PMN) and monocytes at different stages of the disease. Results: we showed that neutrophils and monocytes from HIV-infected patients spontaneously produced increased amounts of H2O2. This increased H2O2 production was associated with alterations of adhesion molecules expression at the cell surface, which also reflected basal activation of phagocytes from the HIV-infected patients. In monocytes, basal H2O2 production correlated with viral load. This increased ROS production was associated with changes in the expression of the antiapoptotic/antioxidant compounds Bcl-2 and thioredoxin along the course of the disease. This modulation could result from a dual regulation by oxidative stress and could explain at least in part why monocyte numbers remain relatively stable throughout the disease. Monocytes expressed a normal maximal capacity to produce ROS in optimal conditions of stimulation. In contrast, after ex vivo priming with TNF alpha or IL-8, neutrophils showed a decreased H2O2 production in response to bacterial N-formyl peptides. This latter impairment correlated with the decrease in CD4 + lymphocyte numbers and with IL-8 and IL-6 plasma levels. Conclusions,ls: the increased basal ROS production by phagocytes could participate to the oxidative injury which has been implicated in the pathophysiology of HIV infection. In addition, the decreased priming of H2O2 production by neutrophils could contribute to the increased susceptibility of HIV-infected patients to bacterial infections. (C) 2001 Elsevier Science B.V. All rights reserved.