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Ambient ultrafine particles activate human monocytes: Effect of dose, differentiation state and age of donors
Environmental Research ( IF 7.7 ) Pub Date : 2017-12-26 , DOI: 10.1016/j.envres.2017.11.019
Bishop Bliss , Kevin Ivan Tran , Constantinos Sioutas , Arezoo Campbell

Exposure to ambient particulate matter (PM) has been linked to adverse pulmonary and cardiovascular health effects. Activation of both inflammatory and oxidative stress pathways has been observed and may be a probable cause of these outcomes. We tested the hypothesis that in human monocytes, PM-induced oxidative and inflammatory responses are interrelated. A human monocytic cell line (THP-1) was used to determine if dose and differentiation state plays a role in the cellular response after a 24hr exposure to particles. Primary human monocytes derived from eight female, non-smoker donors (aged: 21, 24, 27, 28, 48, 49, 54 & 60yo) were used to determine if the age of donors modulates the response. Cells were treated with aqueous suspensions of ambient ultrafine particles (UFP, defined as smaller than 0.2 µm in size) or a media control for 24hr. After exposure, reactive oxygen species (ROS) formation was increased irrespective of dose or differentiation state of THP-1 cells. In the primary human monocytes, ROS formation was not significantly changed. The release of the proinflammatory cytokine, tumor necrosis factor alpha (TNF-α), was dose-dependent and greatest in differentiated compared to undifferentiated THP-1 cells exposed to UFP. In the Primary human monocytes, TNF-α secretion was increased irrespective of the age of the donor. Our results suggest that after a 24hr exposure to particles, general reactive oxygen species formation was nonspecific and uncorrelated to cytokine secretion which was consistently enhanced. Cytokines play an important role in orchestrating many immune responses and thus the ability of ambient particles to enhance robust secretion of a proinflammatory cytokine from primary human monocytes, and how this may influence the response to pathogens and alter disease states, needs to be further evaluated.



中文翻译:

环境超细颗粒激活人单核细胞:剂量,分化状态和供体年龄的影响

暴露于环境颗粒物(PM)与不良的肺部和心血管健康影响有关。已经观察到炎性和氧化应激途径的激活,并且可能是这些结果的可能原因。我们检验了以下假设:在人类单核细胞中,PM诱导的氧化和炎症反应是相互关联的。人类单核细胞系(THP-1)用于确定剂量和分化状态在暴露于颗粒24小时后是否在细胞反应中起作用。来自八名女性非吸烟供者(年龄:21、24、27、28、48、49、54和60岁)的原代人单核细胞用于确定供者的年龄是否调节反应。用环境超细颗粒(UFP,定义为尺寸小于0.2 µm)的水悬浮液或培养基对照处理细胞24小时。暴露后,无论THP-1细胞的剂量或分化状态如何,活性氧(ROS)的形成均增加。在原代人单核细胞中,ROS的形成没有明显改变。与暴露于UFP的未分化THP-1细胞相比,促炎细胞因子肿瘤坏死因子α(TNF-α)的释放是剂量依赖性的,且分化最大。在原代人单核细胞中,不管供体的年龄如何,TNF-α的分泌都会增加。我们的结果表明,暴露于颗粒24小时后,一般活性氧的形成是非特异性的,并且与细胞因子的分泌无关,后者持续增强。

更新日期:2017-12-26
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