BTLA在重症社区获得性肺炎患者中的表达及糖皮质激素干预动物模型的影响

发布时间：2018-04-19 19:11

本文选题：社区获得性肺炎 + BT淋巴衰减子　；参考：《免疫学杂志》2017年04期

【摘要】：目的本研究通过观察BT淋巴衰减子(B and T lymphocyte attenuator,BTLA)在重症CAP患者外周血淋巴细胞及支气管黏膜上的表达,外源性干预LPS-诱导的急性肺部炎症小鼠模型BTLA表达对肺部炎症的作用以及给予糖皮质激素对BTLA表达的影响。方法利用流式细胞学分析重症CAP患者外周血BTLA~+CD4~+淋巴细胞比例,另外对重症CAP患者支气管黏膜常规行HE染色和免疫组织化学检测BTLA表达情况。利用流式细胞学分析LPS诱导的急性肺部炎症模型右心血BTLA~+CD4~+淋巴细胞比例。收集肺泡灌洗液(bronchoalveolar lavage fluid,BALF)行炎症细胞分类计数,并利用ELISA检测炎症因子。取肺组织分别行HE染色、免疫组织化学染色和蛋白印迹。结果流式细胞学分析重症肺炎患者外周血中BTLA~+CD4~+淋巴细胞比例明显高于正常对照组。此外,支气管黏膜HE染色结果显示重症CAP患者支气管黏膜有大量炎症细胞浸润,并且伴有支气管壁增厚;进一步用免疫组织化学检测支气管黏膜BTLA表达,结果提示重症肺炎患者支气管黏膜BTLA表达明显增高,浸润的炎症细胞BTLA表达增高明显。流式细胞学分析LPS诱导的急性肺部炎症模型小鼠右心血中BTLA~+CD4~+淋巴细胞比例明显高于正常对照组。利用激动性抗-BTLA抗体6A6干预急性肺部炎症模型后淋巴细胞BTLA表达较模型小鼠明显增高,同时,激动性抗-BTLA抗体6A6能减轻肺部炎症反应和抑制NF-κB信号通路激活。利用糖皮质激素干预急性肺部炎症模型后淋巴细胞BTLA表达较模型小鼠明显增高,糖皮质激素能减轻肺部炎症反应和抑制NF-κB信号通路激活。结论通过本研究我们推测BTLA信号可能参与了重症CAP患者的免疫调节过程,BTLA可能成为重症CAP治疗的一个新靶点。同时,BTLA的表达可能反应患者机体的免疫状态,为临床使用糖皮质激素治疗提供指导作用。
[Abstract]:Objective to investigate the expression of BT lymphatic attenuated B and T lymphocyte attenuator in peripheral blood lymphocytes and bronchial mucosa of patients with severe CAP. Effects of exogenous intervention on BTLA expression and BTLA expression in acute lung inflammation mice induced by LPS-induced by glucocorticoid. Methods the proportion of BTLA-CD4 ~ lymphocytes in peripheral blood of patients with severe CAP was analyzed by flow cytometry, and the expression of BTLA in bronchial mucosa of patients with severe CAP was detected by HE staining and immunohistochemistry. The ratio of BTLA-CD4 ~ lymphocytes in right heart blood of LPS induced acute pulmonary inflammation model was analyzed by flow cytometry. The alveolar lavage fluid (BALF) was collected and the inflammatory cytokines were detected by ELISA. Lung tissues were stained with HE, immunohistochemistry and Western blot. Results the percentage of BTLA-CD4 ~ lymphocytes in peripheral blood of patients with severe pneumonia was significantly higher than that of normal controls. In addition, the results of HE staining of bronchial mucosa showed that a large number of inflammatory cells were infiltrated in bronchial mucosa and accompanied by bronchial wall thickening in severe patients with CAP, and the expression of BTLA in bronchial mucosa was further detected by immunohistochemistry. The results suggested that the expression of BTLA in bronchial mucosa and BTLA in infiltrated inflammatory cells were significantly increased in patients with severe pneumonia. The percentage of BTLA-CD4 ~ lymphocytes in right heart blood of LPS induced acute pulmonary inflammation model mice was significantly higher than that of normal control group. The expression of lymphocyte BTLA in acute pulmonary inflammation model was significantly increased after intervention of activated anti--BTLA antibody 6A6. Meanwhile, activated anti--BTLA antibody 6A6 could attenuate pulmonary inflammation and inhibit the activation of NF- 魏 B signaling pathway. After glucocorticoid was used to interfere with acute pulmonary inflammation, lymphocyte BTLA expression was significantly higher than that in model mice. Glucocorticoid could attenuate pulmonary inflammation and inhibit the activation of NF- 魏 B signaling pathway. Conclusion in this study, we speculate that BTLA signal may be involved in the immunomodulation process of severe CAP patients. BTLA may be a new target for the treatment of severe CAP. At the same time, the expression of BTLA may reflect the immune state of patients, and provide guidance for clinical use of glucocorticoid therapy.
【作者单位】：遵义市第一人民医院呼吸内科;重庆医科大学第二附属医院呼吸内科;
【基金】：贵州省卫计委科学技术基金(2016-1-018) 遵义市科技计划(遵市科合社〔2016〕04号)
【分类号】：R563.1

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