Microbial translocation is associated with increased monocyte activation and dementia in AIDS patients.
Microbial translocation is associated with increased monocyte activation and dementia in AIDS patients.
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DOI：
10.1371/journal.pone.0002516
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发表时间：
2008-06-25
期刊：
影响因子：
3.7
通讯作者：
Gabuzda D
中科院分区：
文献类型：
--
作者：
Ancuta P;Kamat A;Kunstman KJ;Kim EY;Autissier P;Wurcel A;Zaman T;Stone D;Mefford M;Morgello S;Singer EJ;Wolinsky SM;Gabuzda D
血浆脂多糖(LPS)升高是肠道微生物移位的一个指标，可能是慢性HIV感染中全身免疫激活的原因之一。脂多糖诱导单核细胞活化并转运到脑内，这是HIV相关性痴呆(HAD)发病的关键机制。为确定高水平的内毒素水平是否与单核细胞活化和HAD有关，我们采集了艾滋病患者外周血标本，用凝胶电泳法测定了血浆内毒素，用流式细胞仪检测了外周血单核细胞，用酶联免疫吸附试验检测了单核细胞活化的可溶性标志物。用流式细胞仪分离纯化的单核细胞，用实时荧光定量聚合酶链式反应检测HIV DNA和RNA水平。与CD4+T细胞相比，循环单核细胞表达高水平的激活标记CD69和人类白细胞抗原DR，并且携带较低水平的HIV。高血浆内毒素水平与血浆sCD14和内毒素结合蛋白(LBP)水平升高以及低内毒素核心抗体水平相关。与对照组相比，HAD患者的脂蛋白水平更高，并且与HAD相关，与血浆病毒载量和CD4计数无关。与对照组相比，静脉注射海洛因和/或乙醇或合并丙型肝炎病毒感染的艾滋病患者的脂蛋白水平更高。这些结果表明，内毒素水平升高在推动艾滋病单核细胞活化中发挥了作用，从而促进了HAD的发病，并提供了与药物滥用和丙型肝炎病毒合并感染有关的辅助因素影响这些过程的证据。
Elevated plasma lipopolysaccharide (LPS), an indicator of microbial translocation from the gut, is a likely cause of systemic immune activation in chronic HIV infection. LPS induces monocyte activation and trafficking into brain, which are key mechanisms in the pathogenesis of HIV-associated dementia (HAD). To determine whether high LPS levels are associated with increased monocyte activation and HAD, we obtained peripheral blood samples from AIDS patients and examined plasma LPS by Limulus amebocyte lysate (LAL) assay, peripheral blood monocytes by FACS, and soluble markers of monocyte activation by ELISA. Purified monocytes were isolated by FACS sorting, and HIV DNA and RNA levels were quantified by real time PCR. Circulating monocytes expressed high levels of the activation markers CD69 and HLA-DR, and harbored low levels of HIV compared to CD4+ T-cells. High plasma LPS levels were associated with increased plasma sCD14 and LPS-binding protein (LBP) levels, and low endotoxin core antibody levels. LPS levels were higher in HAD patients compared to control groups, and were associated with HAD independently of plasma viral load and CD4 counts. LPS levels were higher in AIDS patients using intravenous heroin and/or ethanol, or with Hepatitis C virus (HCV) co-infection, compared to control groups. These results suggest a role for elevated LPS levels in driving monocyte activation in AIDS, thereby contributing to the pathogenesis of HAD, and provide evidence that cofactors linked to substance abuse and HCV co-infection influence these processes.
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影响因子：
4.4
作者：
Davidson, Donald J.;Currie, Andrew J.;Speert, David P.
通讯作者：
Speert, David P.
影响因子：
5.5
作者：
Chapoval, AI;Kamdar, SJ;Evans, R
通讯作者：
Evans, R
影响因子：
3.7
作者：
Ancuta, P;Kuntsman, KJ;Gabuzda, D
通讯作者：
Gabuzda, D
影响因子：
56.9
作者：
COHEN, IR;NORINS, LC
通讯作者：
NORINS, LC
影响因子：
29.4
作者：
Dolganiuc, Angela;Norkina, Oxana;Szabo, Gyongyi
通讯作者：
Szabo, Gyongyi