Department of Oral Medicine and Diagnostic Sciences, College of Dentistry, University of Illinois, 801 S. Paulina Street, M/C838, Chicago, IL 60612, USA.
Biomed Pharmacother. 2010 Oct;64(8):572-5. doi: 10.1016/j.biopha.2010.03.005. Epub 2010 May 8.
Neutrophils are endowed with a highly active oxidative metabolism that is crucial for their antimicrobial functions but can produce oxidative conditions disruptive to the host. Opportunistic infections associated with HIV disease and ex vivo studies of neutrophils from HIV patients suggest that neutrophil dysfunctions significantly contribute to HIV disease. The calcium-binding proteins S100A8 and S100A9 are abundant cytosolic constituents of human neutrophils. Our previous work has shown that S100A8 and S100A9 inhibit neutrophil oxidative metabolism. In this study, we tested the hypothesis that neutrophils from HIV infected subjects respond differently to S100A8 and S100A9 when compared to neutrophils isolated from control HIV naive subjects. Neutrophils, freshly isolated from whole blood, were tested in a 96-well plate assay for their ability to oxidize the DCFH-DA probe. The neutrophils from HIV+ and HIV- subjects were stimulated with LPS and inhibited with recombinant S100A8 and S100A9. Our data indicate that when compared to neutrophils isolated from HIV- subjects, neutrophils from HIV+ subjects display an exaggerated response to LPS and a diminished response to S100A8 and S100A9 inhibition. Our data support our hypothesis and signify that, in HIV disease, dysregulated neutrophil responses to endotoxins stimulation and S100A8/A9 inhibition may contribute to a higher risk for oxidative stress associated ailments. The mechanism for the observed differences in neutrophil response and their biological significance in the course of HIV disease should be addressed in further studies.
中性粒细胞具有高度活跃的氧化代谢，这对其抗菌功能至关重要，但也会产生破坏宿主的氧化条件。与 HIV 疾病相关的机会性感染和 HIV 患者中性粒细胞的体外研究表明，中性粒细胞功能障碍显著促进了 HIV 疾病的发生。钙结合蛋白 S100A8 和 S100A9 是人类中性粒细胞丰富的细胞溶质成分。我们之前的工作表明，S100A8 和 S100A9 抑制中性粒细胞的氧化代谢。在这项研究中，我们检验了这样一个假设，即与来自对照 HIV 未感染个体的中性粒细胞相比，HIV 感染个体的中性粒细胞对 S100A8 和 S100A9 的反应不同。从全血中新鲜分离的中性粒细胞在 96 孔板测定中检测其氧化 DCFH-DA 探针的能力。用 LPS 刺激 HIV+和 HIV-的中性粒细胞，并使用重组 S100A8 和 S100A9 抑制它们。我们的数据表明，与来自 HIV-个体的中性粒细胞相比，来自 HIV+个体的中性粒细胞对 LPS 的反应过度，对 S100A8 和 S100A9 抑制的反应减弱。我们的数据支持我们的假设，并表明在 HIV 疾病中，中性粒细胞对内毒素刺激和 S100A8/A9 抑制的失调反应可能导致与氧化应激相关疾病的风险增加。在进一步的研究中，应该解决观察到的中性粒细胞反应差异的机制及其在 HIV 疾病过程中的生物学意义。
