Coal fly ash impairs airway antimicrobial peptides and increases bacterial growth.

Coal fly ash impairs airway antimicrobial peptides and increases bacterial growth.
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DOI:
10.1371/journal.pone.0057673
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发表时间:
2013
期刊:
影响因子:
3.7
通讯作者:
Comellas AP
Comellas AP
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Borcherding JA;Chen H;Caraballo JC;Baltrusaitis J;Pezzulo AA;Zabner J;Grassian VH;Comellas AP

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空气污染是呼吸道感染的危险因素,其主要成分之一是颗粒物(PM),它由许多含铁的颗粒物组成,例如粉煤灰(CFA)。由于游离铁浓度在气道表面液体(ASL)中极低,我们假设CFA损害抗菌肽(AMP)功能,并可能成为细菌的铁源。我们通过向小鼠体内滴注铜绿假单胞菌(PA01)和CFA来测试这一假设,并确定细菌清除的百分比。此外,我们通过将原代人气道上皮细胞暴露于PA01和CFA并测定体外AMP活性和细菌生长来测试细胞培养物中的细菌清除。我们报告说,CFA是细菌的铁的生物可利用的来源。我们表明,CFA干扰细菌清除在体内和原代人气道上皮细胞培养。此外,我们证明CFA在体外抑制AMP活性,我们提出这是我们的细胞培养和体内结果的机制。此外,PA01使用CFA作为铁源,CFA铁溶解和细菌生长之间存在直接相关性。使用的CFA浓度与人类日常暴露量非常相关,因此对易感受试者构成潜在的公共卫生风险。虽然CFA为细菌提供了生物可利用铁的来源,但并非所有CFA颗粒都具有相同的生物效应,并且它们对铁溶解的倾向是一个重要因素。CFA损害肺部细菌清除的先天免疫机制,特别是AMP活性。我们预计,确定呼吸道感染的PM机制将转化为旨在控制的公共卫生政策,不仅是PM暴露的浓度,而且是可能导致易感个体和人群呼吸道感染的理化特性。
Air pollution is a risk factor for respiratory infections, and one of its main components is particulate matter (PM), which is comprised of a number of particles that contain iron, such as coal fly ash (CFA). Since free iron concentrations are extremely low in airway surface liquid (ASL), we hypothesize that CFA impairs antimicrobial peptides (AMP) function and can be a source of iron to bacteria. We tested this hypothesis in vivo by instilling mice with Pseudomonas aeruginosa (PA01) and CFA and determine the percentage of bacterial clearance. In addition, we tested bacterial clearance in cell culture by exposing primary human airway epithelial cells to PA01 and CFA and determining the AMP activity and bacterial growth in vitro. We report that CFA is a bioavailable source of iron for bacteria. We show that CFA interferes with bacterial clearance in vivo and in primary human airway epithelial cultures. Also, we demonstrate that CFA inhibits AMP activity in vitro, which we propose as a mechanism of our cell culture and in vivo results. Furthermore, PA01 uses CFA as an iron source with a direct correlation between CFA iron dissolution and bacterial growth. CFA concentrations used are very relevant to human daily exposures, thus posing a potential public health risk for susceptible subjects. Although CFA provides a source of bioavailable iron for bacteria, not all CFA particles have the same biological effects, and their propensity for iron dissolution is an important factor. CFA impairs lung innate immune mechanisms of bacterial clearance, specifically AMP activity. We expect that identifying the PM mechanisms of respiratory infections will translate into public health policies aimed at controlling, not only concentration of PM exposure, but physicochemical characteristics that will potentially cause respiratory infections in susceptible individuals and populations.
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