Human Serum Albumin (HSA) Suppresses the Effects of Glycerol Monolaurate (GML) on Human T Cell Activation and Function
Human Serum Albumin (HSA) Suppresses the Effects of Glycerol Monolaurate (GML) on Human T Cell Activation and Function
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DOI：
10.1371/journal.pone.0165083
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发表时间：
2016-10-20
期刊：
影响因子：
3.7
通讯作者：
Houtman, Jon C. D.
中科院分区：
文献类型：
--
作者：
Zhang, Michael S.;Houtman, Jon C. D.
月桂酸甘油单酯(GML)是一种具有良好抗微生物特性的单甘油酯。由于这些特性，GML被广泛用于食品、化妆品和个人护理产品，目前正被测试为治疗月经相关性中毒性休克综合征、浅表伤口感染和艾滋病毒传播的药物。最近，我们描述了GML有效地抑制选择性T细胞受体(TCR)诱导的信号事件，导致人类T细胞效应器功能降低。然而，血液和感染部位存在的可溶性宿主因子如何影响GML介导的人类T细胞抑制尚不清楚。在这项研究中，我们研究了人血清白蛋白(HSA)如何影响GML诱导的人T细胞抑制。我们发现，HSA和其他血清蛋白以低微摩尔亲和力与GML的12个碳酰基侧链结合，并恢复TCR诱导的质膜上LAT、PLC-Gamma 1和AKT微簇的形成。此外，HSA逆转了GML对AKT磷酸化的抑制，并部分恢复了GML处理细胞中细胞因子的产生。我们的数据显示，HSA是人类血清和感染部位最丰富的蛋白质之一，它有效地逆转了GML对人类T细胞的抑制。这表明GML驱动的人类T细胞抑制依赖于局部组织环境，白蛋白浓度是GML功能的主要决定因素。
Glycerol monolaurate (GML) is a monoglyceride with well characterized anti-microbial properties. Because of these properties, GML is widely used in food, cosmetics, and personal care products and currently being tested as a therapeutic for menstrual associated toxic shock syndrome, superficial wound infections, and HIV transmission. Recently, we have described that GML potently suppresses select T cell receptor (TCR)-induced signaling events, leading to reduced human T cell effector functions. However, how soluble host factors present in the blood and at sites of infection affect GML-mediated human T cell suppression is unknown. In this study, we have characterized how human serum albumin (HSA) affects GML-induced inhibition of human T cells. We found that HSA and other serum albumins bind to 12 carbon acyl side chain of GML at low micromolar affinities and restores the TCR-induced formation of LAT, PLC-gamma 1, and AKT microclusters at the plasma membrane. Additionally, HSA reverses GML mediated inhibition of AKT phosphorylation and partially restores cytokine production in GML treated cells. Our data reveal that HSA, one of the most abundant proteins in the human serum and at sites of infections, potently reverses the suppression of human T cells by GML. This suggests that GML-driven human T cell suppression depends upon the local tissue environment, with albumin concentration being a major determinant of GML function.