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甲苯二异氰酸酯诱导哮喘的小鼠模型中的免疫决定因素。

Immunological determinants in a murine model of toluene diisocyanate-induced asthma.

机构信息

Centre of Occupational Allergy and Environmental Health, Nofer Institute of Occupational Medicine, Łódź, Poland.

出版信息

Int J Occup Med Environ Health. 2012 Sep;25(4):492-8. doi: 10.2478/s13382-012-0063-1. Epub 2012 Nov 24.

DOI:10.2478/s13382-012-0063-1
PMID:23184444
Abstract

OBJECTIVES

Diisocyanates (DIC) are highly reactive, low-molecular-weight chemicals which are the leading cause of occupational asthma (OA). The aim of the study was to analyze certain aspects of the pathogenesis of allergic inflammation in the airways induced by toluene diisocyanate (TDI) in an experimental model in mice.

MATERIALS AND METHODS

The experiment was carried out on 50 female BALB/cJ/Han/IMP mice, which were exposed by inhalation (intranasal and in the inhalation chamber) to toluene diisocyanate (2,4-TDI). After the experiment, the bronchoalveolar lavage fluid (BALF) was collected from the animals, and the composition of the induced inflammatory cells, and the concentrations of certain cytokines (IL-4, IL-5, TNF-α) were evaluated.

RESULTS

The total number of cells in BALF of the examined group of mice was significantly higher compared to the control mice. There was also a significant increase in neutrophils and eosinophils in the study group compared to the controls. The number of lymphocytes and macrophages did not differ significantly between the two groups. A statistically significant increase in the level of TNF-α was shown to occur in the group exposed to toluene diisocyanate in comparison to the control group. The concentration of IL-4 increased in the study group, compared to the control one, but the differences did not reach the level of significance, p > 0.05. Such difference was not observed for IL-5.

CONCLUSIONS

We developed a murine model of TDI-induced asthma which caused the influx of inflammatory cells like eosinophils and neutrophils in the bronchoalveolar lavage fluid (BALF) in the TDI-treated mice. The increase of the concentration of some proinflammatory cytokines (TNF-α, IL-4) in BALF from the exposed mice was also observed.

摘要

目的

二异氰酸酯(DIC)是一种高度反应性、低分子量的化学物质,是职业性哮喘(OA)的主要原因。本研究的目的是分析甲苯二异氰酸酯(TDI)在实验性小鼠模型中诱导气道过敏炎症发生的某些发病机制。

材料与方法

实验在 50 只雌性 BALB/cJ/Han/IMP 小鼠中进行,这些小鼠通过吸入(鼻内和吸入室)甲苯二异氰酸酯(2,4-TDI)进行暴露。实验后,从动物中收集支气管肺泡灌洗液(BALF),评估诱导炎症细胞的组成和某些细胞因子(IL-4、IL-5、TNF-α)的浓度。

结果

与对照组相比,实验组小鼠 BALF 中的总细胞数明显升高。与对照组相比,实验组中的中性粒细胞和嗜酸性粒细胞也明显增加。两组之间的淋巴细胞和巨噬细胞数量没有显著差异。与对照组相比,暴露于甲苯二异氰酸酯的组中 TNF-α 的水平显示出统计学上的显著增加。与对照组相比,研究组中 IL-4 的浓度增加,但差异没有达到显著水平,p>0.05。对于 IL-5 则没有观察到这种差异。

结论

我们开发了一种 TDI 诱导的哮喘小鼠模型,该模型导致实验组小鼠支气管肺泡灌洗液(BALF)中炎症细胞如嗜酸性粒细胞和中性粒细胞的流入。还观察到暴露于 TDI 的小鼠 BALF 中某些促炎细胞因子(TNF-α、IL-4)浓度的增加。

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