Elevation of plasma thioredoxin levels in HIV-infected individuals

Elevation of plasma thioredoxin levels in HIV-infected individuals
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DOI:
10.1093/intimm/8.4.603
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发表时间:
1996-04-01
影响因子:
4.4
通讯作者:
Herzenberg, LA
Herzenberg, LA
中科院分区:
医学3区
文献类型:
--
作者:
Nakamura, H;DeRosa, S;Herzenberg, LA

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被引文献

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硫氧还蛋白(Trx)是一种广泛存在的蛋白质,与氧化还原和蛋白质二硫键还原密切相关,已被证明可从细胞中释放并具有类精氨酸活性。此外,Trx与免疫应答的氧化还原调节有关,并且显示在来自AIDS患者的组织中是缺乏的。在本文呈现的研究中,通过ELISA测量来自HIV感染个体(n = 136)和HIV阴性对照(n = 47)的血浆样品中的血浆Trx水平。根据血浆样品中血红蛋白的水平校正Trx测量值。所提供的数据显示,与组织Trx水平相反,HIV感染个体中校正的血浆Trx水平显著高于对照组(P < 0.0001)。此外,所研究的HIV感染个体中,约25%的血浆Trx水平高于对照组中发现的最高水平(37 ng/ml)。对感染个体的外周血单核细胞(PBMC)进行的详细多参数FAGS分析表明,血浆Trx水平较高(37 ng/ml或更高)的个体倾向于具有较低的总体CD 4计数。此外,血浆Trx水平的增加与一氯二亚胺染色的减少(表明PBMC中细胞内谷胱甘肽水平较低)和HIV感染后期发生的表面抗原表达(CD 62 L、CD 38和CD 20)的变化相关。这些相关性表明,血浆Trx水平的升高可能是晚期HIV疾病的重要组成部分,可能与此阶段经常发生的氧化应激有关。
Thioredoxin (Trx), a ubiquitous protein intimately involved in redox and protein disulfide reductions, has been shown to be released from cells and to have cytokine-like activities. In addition, Trx has been implicated in the redox regulation of immunological responses and shown to be deficient in tissues from AIDS patients, In studies presented here, plasma Trx levels were measured by ELISA in plasma samples from HIV-infected individuals (n = 136) and HIV-negative controls (n = 47), To account for the release of Trx into plasma due to hemolysis, the Trx measurements were corrected according to the level of hemoglobin in the plasma sample. Data presented show that, in contrast to tissue Trx levels, corrected plasma Trx levels are significantly higher in HIV-infected individuals than in controls (P < 0.0001). furthermore, similar to 25% of the HIV-infected individuals studied have plasma Trx levels greater than the highest level found in controls (37 ng/ml), Detailed multiparameter FAGS analysis of peripheral blood mononuclear cells (PBMC) from the infected individuals demonstrates that those with higher plasma Trx levels (37 ng/ml or greater) tend to have lower overall CD4 counts. In addition, increases in plasma Trx levels correlate with decreases in monochlorobimane staining (indicative of lower intracellular glutathione levels in PBMC) and with changes in surface antigen expression (CD62L, CD38 and CD20) that occur in the later stages of HIV infection. These correlations suggest that elevation of plasma Trx levels may be an important component of advanced HIV disease, perhaps related to the oxidative stress that often occurs at this stage.