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通过蛋白质组学差异显示鉴定新生儿单核细胞中的免疫缺陷分子。

Identification of immunodeficient molecules in neonatal mononuclear cells by proteomic differential displays.

机构信息

Department of Pediatrics, Kaohsiung Chang Gung Memorial Hospital, Graduate Institute of Clinical Medical Sciences, Chang Gung University College of Medicine, Kaohsiung, Taiwan.

出版信息

Proteomics. 2011 Sep;11(17):3491-500. doi: 10.1002/pmic.201100123. Epub 2011 Aug 4.

Abstract

Human newborns are known to be susceptible to microbial infection. This susceptibility is generally attributed to immaturity of the newborn immune system. However, the mechanisms for impaired immunity in newborns are still incompletely defined. In this study, we sought to elucidate the protein differential display between adult and neonatal mononuclear cells (MNC) using a proteomic approach. MNC samples from cord blood and adult peripheral blood were subjected to 2-D PAGE analysis. Differential protein displays between cord blood and adult MNC were determined and validated. There were 34 differentially expressed proteins between cord blood and adult MNC identified by 2-D PAGE. The differentially displayed proteins were clustered into two major signal pathways, cellular processing and purine metabolism. After validation by Western blot, we found more abundant arginase-1 (ARG1) and Rho GDP-dissociation inhibitor 2 (RhoGDI2), while less adenosine deaminase (ADA) and β-actin in cord blood MNC. In functional validation, we found that lower ADA was proven to enhance the TNF-α production by cord blood monocytes. The results from this study discovered the proteomic displays for altered immunity between adult and neonatal MNC that support a understanding of the correction of impaired immune response in newborns.

摘要

人类新生儿易受微生物感染。这种易感性通常归因于新生儿免疫系统的不成熟。然而,新生儿免疫功能受损的机制仍不完全明确。在这项研究中,我们试图采用蛋白质组学方法阐明成人和新生儿单核细胞(MNC)之间的蛋白差异表达。对脐血和成人外周血的 MNC 样本进行 2-D PAGE 分析。确定并验证了脐血和成人 MNC 之间的差异蛋白表达。通过 2-D PAGE 鉴定出 34 种脐血和成人 MNC 之间差异表达的蛋白质。差异表达的蛋白质被聚类为两个主要信号通路,细胞处理和嘌呤代谢。通过 Western blot 验证后,我们发现脐血 MNC 中精氨酸酶 1(ARG1)和 Rho GDP 解离抑制剂 2(RhoGDI2)更丰富,而腺苷脱氨酶(ADA)和 β-肌动蛋白较少。在功能验证中,我们发现降低 ADA 可增强脐血单核细胞产生 TNF-α。这项研究的结果发现了成人和新生儿 MNC 之间改变的免疫的蛋白质组学表现,这有助于理解纠正新生儿免疫应答受损。

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