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致死性哮喘患者支气管肺淋巴结与大气道细胞迁移。

Bronchopulmonary lymph nodes and large airway cell trafficking in patients with fatal asthma.

机构信息

Department of Pathology, São Paulo University Medical School, São Paulo, Brazil.

Department of Pathology, São Paulo University Medical School, São Paulo, Brazil.

出版信息

J Allergy Clin Immunol. 2015 May;135(5):1352-7.e1-9. doi: 10.1016/j.jaci.2014.08.021. Epub 2014 Sep 26.

Abstract

BACKGROUND

Immune responses in asthmatic patients involve coordinated cellular responses in the airways and lymph nodes (LNs). However, no studies have described the composition of different cell populations in the bronchopulmonary LNs of asthmatic patients.

OBJECTIVE

We sought to investigate the expression of dendritic cells (DCs) and costimulatory molecules, B cells, T cells, TH2-related cytokines, eosinophils, and vascular cell adhesion molecule in the bronchopulmonary LNs and large airways of asthmatic patients.

METHODS

Using histochemistry, immunohistochemistry, and image analysis, we investigated the expression of Factor XIIIa(+), CD1a(+), CD83(+), and CD207(+) DCs; CD4(+) and CD8(+) T cells; CD20(+) B cells; CD23(+) (FcεRII) cells; IL-4; IL-5; eosinophils, and vascular cell adhesion molecule 1 in the large airways and bronchopulmonary LNs of 11 nonsmokers who died from an asthma exacerbation (fatal asthma [FA]) in comparison with 8 nonasthmatic control subjects. In selected cases of FA, we analyzed the coexpression of HLA-DR, CD40, and CD80 in lung and LN eosinophils.

RESULTS

The LNs of asthmatic patients exhibited increased density of eosinophils. No other cells were expressed differently in the LNs of patients with FA. The large airways of patients with FA had increased expression of eosinophils in all layers and increased expression of Factor XIIIa(+) cells, CD4(+) and CD8(+) T cells, CD20(+) B cells, and CD23(+) cells in the outer layer. There was colocalization of HLA-DR, CD40, and CD80 in the eosinophils at both sites.

CONCLUSIONS

FA is associated with the increased presence of eosinophils in the LNs and large airways, which express HLA-DR and costimulatory molecules. The expression of Factor XIIIa(+) monocyte-derived DCs, CD4(+) and CD8(+) T cells, CD20(+) B cells, and CD23(+) cells was increased in the large airways without a corresponding increase in the expression of these cells in the bronchopulmonary LNs. These findings support the concept that eosinophils might act as antigen-presenting cells in patients with FA.

摘要

背景

哮喘患者的免疫反应涉及气道和淋巴结(LN)中的细胞协同反应。然而,目前尚无研究描述哮喘患者支气管肺 LN 中不同细胞群的组成。

目的

我们旨在研究哮喘患者支气管肺 LN 和大气道中树突状细胞(DC)和共刺激分子、B 细胞、T 细胞、TH2 相关细胞因子、嗜酸性粒细胞和血管细胞黏附分子的表达。

方法

通过组织化学、免疫组织化学和图像分析,我们研究了 11 例非吸烟者因哮喘恶化(致死性哮喘[FA])死亡患者与 8 例非哮喘对照者支气管肺 LN 和大气道中 Factor XIIIa(+)、CD1a(+)、CD83(+)和 CD207(+)DC、CD4(+)和 CD8(+)T 细胞、CD20(+)B 细胞、CD23(+)(FcεRII)细胞、IL-4、IL-5、嗜酸性粒细胞和血管细胞黏附分子 1 的表达。在 FA 的某些病例中,我们分析了肺和 LN 嗜酸性粒细胞中 HLA-DR、CD40 和 CD80 的共表达。

结果

哮喘患者的 LN 中嗜酸性粒细胞密度增加。FA 患者的 LN 中未表达其他不同的细胞。FA 患者的大气道各层均有嗜酸性粒细胞表达增加,外层有 Factor XIIIa(+)细胞、CD4(+)和 CD8(+)T 细胞、CD20(+)B 细胞和 CD23(+)细胞表达增加。在外层,HLA-DR、CD40 和 CD80 在嗜酸性粒细胞中存在共定位。

结论

FA 与 LN 和大气道中嗜酸性粒细胞的增加有关,这些细胞表达 HLA-DR 和共刺激分子。大气道中 Factor XIIIa(+)单核细胞衍生的 DC、CD4(+)和 CD8(+)T 细胞、CD20(+)B 细胞和 CD23(+)细胞的表达增加,但支气管肺 LN 中这些细胞的表达没有相应增加。这些发现支持了嗜酸性粒细胞可能在 FA 患者中充当抗原呈递细胞的概念。

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