Elbim C, Pillet S, Prevost M H, Preira A, Girard P M, Rogine N, Hakim J, Israel N, Gougerot-Pocidalo M A
INSERM U 479 and Service d'Immunologie et d'Hématologie, CHU X. Bichat, 46 rue Henri Huchard, 75877 Paris Cedex, France.
J Clin Virol. 2001 Feb;20(3):99-109. doi: 10.1016/s1386-6532(00)00133-5.
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.
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.
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 TNFalpha 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.
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.
为应对多种刺激，吞噬细胞会释放大量活性氧（ROS），这对于杀灭细菌至关重要。然而，抗氧化分子未能适当补偿过量产生的ROS会导致氧化应激，这在HIV感染的发病机制中可能也起重要作用。事实上，ROS参与慢性炎症、HIV复制以及免疫系统细胞的凋亡。
我们使用流式细胞术研究全血中疾病不同阶段多形核中性粒细胞（PMN）和单核细胞的活化及氧化还原状态。
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H2O2量增加。这种H2O2产生量的增加与细胞表面黏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情况。在单核细胞中，基础H2O2产生量与病毒载量相关。疾病过程中，这种ROS产生量的增加与抗凋亡/抗氧化化合物Bcl-2和硫氧还蛋白表达的变化有关。这种调节可能是由氧化应激的双重调节导致的，并且至少可以部分解释为什么整个疾病过程中单核细胞数量保持相对稳定。单核细胞在最佳刺激条件下表现出产生ROS的正常最大能力。相比之下，用TNFα或IL-8进行体外预刺激后，中性粒细胞对细菌N-甲酰肽的反应中H2O2产生量减少。后一种损伤与CD4+淋巴细胞数量的减少以及IL-8和IL-6血浆水平相关。
吞噬细胞基础ROS产生量的增加可能参与了与HIV感染病理生理学相关的氧化损伤。此外，中性粒细胞H2O2产生的预刺激减少可能导致HIV感染患者对细菌感染的易感性增加。
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