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在哮喘患者和健康个体中,从畜牧场的颗粒物质的体外先天反应。

Ex vivo innate responses to particulate matter from livestock farms in asthma patients and healthy individuals.

机构信息

Department of Respiratory Medicine, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.

Department of Experimental Immunology (Amsterdam Infection & Immunity Institute), Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.

出版信息

Environ Health. 2020 Jul 3;19(1):78. doi: 10.1186/s12940-020-00632-8.

Abstract

BACKGROUND

Asthma patients suffer from periodic acute worsening of symptoms (i.e. loss of asthma control or exacerbations), triggered by a variety of exogenous stimuli. With the growing awareness that air pollutants impact respiratory diseases, we investigated whether particulate matter (PM) derived from various livestock farms (BioPM) differentially affected innate and oxidative stress responses in asthma and health.

METHODS

Peripheral blood mononuclear cells (PBMCs), collected from patients sequentially before and during loss of asthma control and from healthy individuals, were exposed to BioPM collected from chicken, goat and pig farms (1 and 5 μg/ml), with or without pre-treatment with antioxidants. Cytokine release and oxidative stress were assessed.

RESULTS

PBMCs produced IFNγ, IL-1β, IL-10 and TNFα upon stimulation with BioPM, with that from pig farms inducing the highest cytokine levels. Overall, cytokine production was irrespective of the presence or state of disease. However, PBMCs from stable asthma patients upon exposure to the three BioPM showed more extreme TNFα responses than those from healthy subjects. Furthermore, PBMCs obtained during loss of asthma control that were exposed to BioPM from pig farms showed enhanced IFNγ release as well as decreased oxidative stress levels upon pre-treatment with N-acetylcysteine (NAC) compared to stable disease. NAC, but not superoxide dismutase and catalase, also counteracted BioPM-induced cytokine release, indicating the importance of intracellular reactive oxygen species in the production of cytokines.

CONCLUSIONS

BioPM triggered enhanced pro-inflammatory responses by PBMCs from both healthy subjects and asthma patients, with those from patients during loss of asthma control showing increased susceptibility to BioPM from pig farms in particular.

摘要

背景

哮喘患者会周期性地出现症状急性恶化(即哮喘控制丧失或恶化),这是由各种外源性刺激引发的。由于人们越来越意识到空气污染物会影响呼吸道疾病,我们研究了来自不同养殖场的颗粒物(BioPM)是否会对哮喘和健康人群的固有和氧化应激反应产生不同影响。

方法

我们从哮喘控制丧失前和丧失期间以及健康个体中依次采集外周血单核细胞(PBMCs),并用来自鸡、山羊和猪圈的 BioPM(1 和 5μg/ml)对其进行刺激,同时用或不用抗氧化剂预处理。评估细胞因子释放和氧化应激情况。

结果

BioPM 刺激 PBMCs 产生 IFNγ、IL-1β、IL-10 和 TNFα,其中来自猪圈的 BioPM 诱导的细胞因子水平最高。总体而言,细胞因子的产生与疾病的存在或状态无关。然而,与健康个体相比,暴露于三种 BioPM 的稳定哮喘患者的 PBMCs 产生的 TNFα 反应更为剧烈。此外,在哮喘控制丧失期间采集的 PBMCs 在暴露于来自猪圈的 BioPM 时,与稳定疾病相比,用 N-乙酰半胱氨酸(NAC)预处理后 IFNγ 释放增加,氧化应激水平降低。与超氧化物歧化酶和过氧化氢酶不同,NAC 也可以抵消 BioPM 诱导的细胞因子释放,表明细胞内活性氧在细胞因子产生中的重要性。

结论

BioPM 可引发健康个体和哮喘患者的 PBMCs 产生更强的促炎反应,尤其是在哮喘控制丧失期间,来自患者的 PBMCs 对来自猪圈的 BioPM 更为敏感。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d929/7333268/1d8d5c5d2739/12940_2020_632_Fig1_HTML.jpg

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