The response of a co-culture lung model to fine and ultrafine particles of incinerator fly ash at the air-liquid interface

The response of a co-culture lung model to fine and ultrafine particles of incinerator fly ash at the air-liquid interface
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DOI:
10.1177/026119290803600306
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发表时间:
2008-07-01
影响因子:
2.7
通讯作者:
Krug, Harald F.
Krug, Harald F.
中科院分区:
医学4区
文献类型:
--
作者:
Diabate, Silvia;Muelhopt, Sonja;Krug, Harald F.

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环境大气中颗粒物浓度的升高对人类健康构成潜在风险。因此,有必要进行基于细胞的体外试验,以评估吸入颗粒物排放的毒理学潜力。在这项研究中,在空气-液体界面处的共培养细胞模型的暴露被用于评估测试气溶胶的剂量依赖性生物效应。该系统用于将人类细胞暴露于与环境相关的气溶胶中,该气溶胶由商业城市垃圾焚烧炉中收集的飞灰产生并重新悬浮在过滤空气中。在生物测定中使用与在Transwell插入物上生长的分化的THP-1巨噬细胞共培养的人支气管上皮细胞BEAS-2B。进行细胞活力、白细胞介素-8(IL-8)释放、细胞内谷胱甘肽和血红素加氧酶-1酶表达的分析。细胞运输和暴露于加湿过滤空气或试验气雾剂(100 ml/min)1至6小时,细胞耐受良好,对其活力无影响。IL-8的释放和血红素氧合酶-1的表达水平升高暴露于飞灰气溶胶作为时间的函数,但不是暴露于清洁空气。对于IL-8释放,假设颗粒的沉积质量与暴露时间相关,证明了剂量依赖性效应。暴露于测试气溶胶不影响细胞内谷胱甘肽浓度。这种体外方法比浸没暴露更真实地模拟了人体肺部的颗粒沉积,并且保留了颗粒的固有特性。它显示出用于检测可能对人类健康有害的颗粒物排放的前景。
Elevated concentrations of particulate matter in the environmental atmosphere constitute a potential risk to human health. In vitro cell-based assays are therefore necessary to evaluate the toxicological potential of inhaled particulate emissions. In this study, the exposure of a co-culture cell model at the air-liquid interface was used to evaluate the dose-dependent biological effects of a test aerosol. The CULTEX (R) system was used to expose human cells to an environmentally-relevant aerosol, generated from fly ash collected in a commercial municipal waste incinerator and resuspended in filtered air. Human bronchial epithelial cells, BEAS-2B, co-cultured with differentiated THP-1 macrophages growing on Transwell (R) inserts, were employed in the bioassay. Analyses of cell viability, interleukin-8 (IL-8) release, intracellular glutathione, and haeme oxygenase-1 enzyme expression were performed. Transportation of the cells and exposure to humidified filtered air or the test aerosol, at 100ml/min for 1 to 6 hours, were well tolerated by the cells and had no effect on their viability. Levels of IL-8 release and haeme oxygenase-1 expression were elevated by exposure to fly ash aerosol as a function of time, but not by exposure to clean air. For IL-8 release, a dose-dependent effect was demonstrated with the assumption that the deposited mass of the particles correlated with exposure time. Exposure to the test aerosol did not affect the intracellular glutathione concentration. This in vitro approach simulates particle deposition in the human lung more realistically than does submerged exposure, and it preserves the inherent properties of the particles. It shows promise for use to detect particulate emissions which are potentially detrimental to human health.