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静脉注射免疫球蛋白对铜绿假单胞菌肺炎免疫抑制小鼠来源的调节性T细胞功能的影响

Effect of intravenous immunoglobulin on the function of Treg cells derived from immunosuppressed mice with Pseudomonas aeruginosa pneumonia.

作者信息

Li Junlu, Chen Tingsang, Yuan Congcong, Zhao Guoqiang, Xu Min, Li Xiaoyan, Cao Jie, Xing Lihua

机构信息

Department of Respiratory Intensive Care Unit (RICU), The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.

School of basic medical sciences, Zhengzhou University, Zhengzhou, Henan, China.

出版信息

PLoS One. 2017 May 8;12(5):e0176843. doi: 10.1371/journal.pone.0176843. eCollection 2017.

DOI:10.1371/journal.pone.0176843
PMID:28481908
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5421750/
Abstract

AIM

The present study aimed to investigate the effect of intravenous immunoglobulin (IVIG) on regulatory T (Treg) cells derived from immunosuppressed mice with Pseudomonas aeruginosa (PA) pneumonia.

METHODS

A total of 108 BALB/c mice were randomly divided into the following groups: control group (Control), immunosuppressed group (IS), PA pneumonia group (PA), PA pneumonia in immunosuppressed group (IS + PA), PA pneumonia with IVIG treatment in immunocompetent group (PA + IVIG) and PA pneumonia with IVIG treatment in immunosuppressed group (IS + PA + IVIG). Each group comprised 18 mice. The combined PA pneumonia in immunosuppressed model and the treatment models were established. The mice in each group were sacrificed at 4, 8, and 24 h time points. The general condition and pathological changes in the lung tissues of the mice were monitored. Reverse transcription-polymerase chain reaction was used to detect the forkhead box P3 (FOXP3) mRNA relative expression level in the lung tissues. The enzyme-linked immunosorbent assay was used to detect the serum concentration of active transforming growth factor beta (TGF-β).

RESULTS

No inflammatory response were exhibited in the lung tissues of the mice in Control group and IS group, while varying degrees of acute lung injury were revealed in the mice in PA group, IS + PA group, PA + IVIG group and IS + PA + IVIG group. Lung tissue injury was most apparent at the 8 h time point, and it indicated the greatest effect in IS + PA group. Whereas tissue damages were alleviated in PA + IVIG group and IS + PA + IVIG group compared with IS + PA group. In addition, tissue damage lessened in PA + IVIG group compared with PA group and IS + PA + IVIG group. FOXP3 mRNA expression levels in the lung tissues and the serum concentration of TGF-β were lower in IS group, PA group, IS + PA group and IS + PA + IVIG group at the 4, 8 and 24 h time points, respectively compared with Control group. FOXP3 mRNA expression levels decreased in PA + IVIG group at the 4h time point and TGF-β serum concentrations decreased at the 4 and 8h time points compared with Control group, and subsequently increased.

CONCLUSIONS

In the immunosuppred model with PA pneumonia, the immune system was greatly compromised. IVIG partially restored the immunosuppressed functions of Treg cells, suppressed the overactivated immune system and ameliorated the development of the disease.

摘要

目的

本研究旨在探讨静脉注射免疫球蛋白(IVIG)对铜绿假单胞菌(PA)肺炎免疫抑制小鼠来源的调节性T(Treg)细胞的影响。

方法

将108只BALB/c小鼠随机分为以下几组:对照组(Control)、免疫抑制组(IS)、PA肺炎组(PA)、免疫抑制小鼠PA肺炎组(IS + PA)、免疫健全小鼠PA肺炎IVIG治疗组(PA + IVIG)和免疫抑制小鼠PA肺炎IVIG治疗组(IS + PA + IVIG)。每组18只小鼠。建立免疫抑制模型合并PA肺炎及治疗模型。在4、8和24小时时间点处死每组小鼠。监测小鼠的一般状况和肺组织的病理变化。采用逆转录-聚合酶链反应检测肺组织中叉头框P3(FOXP3)mRNA相对表达水平。采用酶联免疫吸附测定法检测血清中活性转化生长因子β(TGF-β)的浓度。

结果

对照组和IS组小鼠肺组织无炎症反应,而PA组、IS + PA组、PA + IVIG组和IS + PA + IVIG组小鼠出现不同程度的急性肺损伤。肺组织损伤在8小时时间点最为明显,且在IS + PA组中影响最大。与IS + PA组相比,PA + IVIG组和IS + PA + IVIG组的组织损伤有所减轻。此外,与PA组和IS + PA + IVIG组相比,PA + IVIG组的组织损伤减轻。与对照组相比,IS组、PA组、IS + PA组和IS + PA + IVIG组在4、8和24小时时间点肺组织中FOXP3 mRNA表达水平及血清TGF-β浓度分别较低。与对照组相比,PA + IVIG组在4小时时间点FOXP3 mRNA表达水平降低,在4和8小时时间点TGF-β血清浓度降低,随后升高。

结论

在PA肺炎免疫抑制模型中,免疫系统受到严重损害。IVIG部分恢复了Treg细胞的免疫抑制功能,抑制了过度激活的免疫系统,改善了疾病的发展。

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