Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE, USA.
Proteomics Clin Appl. 2010 Sep;4(8-9):706-14. doi: 10.1002/prca.201000010.
Monocyte ingress into the brain during progressive human immunodeficiency virus (HIV-1) infection parallels the severity of cognitive impairments. Although activated monocyte phenotypes emerge in disease, the functional correlates of these cells remain unresolved.
To this end, we studied the proteome of blood-derived monocytes obtained from Hispanic women with the most severe form of HIV-associated neurocognitive disorders, HIV-associated dementia (HAD). Monocytes isolated from peripheral blood mononuclear cells by CD14+ immunoaffinity column chromatography were >95% pure. Cells were recovered from four patients without evidence of cognitive impairment and five with HAD and analyzed by 2-D DIGE and tandem MS.
Importantly, ADP ribosylhydrolase, myeloperoxidase, thioredoxin, peroxiredoxin 3, NADPH, and GTPase-activating protein were all downregulated in HAD. In regards to myeloperoxidase, thioredoxin, and peroxiredoxin 3, these changes were validated in an additional cohort of 30 patients by flow cytometry.
We conclude that deficits in monocyte antioxidants lead to neuronal damage through the loss of hydrogen peroxide scavenging capabilities; thus exposing neurons to apoptosis-inducing factors. Altered monocyte functions therefore may contribute to the development and progression of cognitive impairment.
在进行性人类免疫缺陷病毒 (HIV-1) 感染期间，单核细胞进入大脑与认知障碍的严重程度相平行。尽管在疾病中出现了激活的单核细胞表型，但这些细胞的功能相关性仍未解决。
为此，我们研究了来自具有 HIV 相关神经认知障碍（HIV 相关痴呆症，HAD）最严重形式的西班牙裔妇女血液中分离的单核细胞的蛋白质组。通过 CD14+免疫亲和柱色谱法从外周血单核细胞中分离的单核细胞纯度>95%。从四个没有认知障碍证据的患者和五个 HAD 患者中分离细胞，并通过 2-D DIGE 和串联 MS 进行分析。
重要的是，ADP 核糖基水解酶、髓过氧化物酶、硫氧还蛋白、过氧化物酶 3、NADPH 和 GTP 酶激活蛋白在 HAD 中均下调。关于髓过氧化物酶、硫氧还蛋白和过氧化物酶 3，这些变化在另外 30 名患者的队列中通过流式细胞术得到了验证。
我们得出结论，单核细胞抗氧化剂的缺陷导致神经元损伤，通过丧失过氧化氢清除能力；从而使神经元暴露于诱导凋亡的因子中。因此，单核细胞功能的改变可能有助于认知障碍的发展和进展。
