Gojova Andrea, Guo Bing, Kota Rama S, Rutledge John C, Kennedy Ian M, Barakat Abdul I
Department of Mechanical and Aeronautical Engineering, University of California, Davis, Davis, California, USA.
Environ Health Perspect. 2007 Mar;115(3):403-9. doi: 10.1289/ehp.8497. Epub 2006 Dec 11.
The mechanisms governing the correlation between exposure to ultrafine particles and the increased incidence of cardiovascular disease remain unknown. Ultrafine particles appear to cross the pulmonary epithelial barrier into the bloodstream, raising the possibility of direct contact with the vascular endothelium.
Because endothelial inflammation is critical for the development of cardiovascular pathology, we hypothesized that direct exposure of human aortic endothelial cells (HAECs) to ultrafine particles induces an inflammatory response and that this response depends on particle composition.
To test the hypothesis, we incubated HAECs for 1-8 hr with different concentrations (0.001-50 mug/mL) of iron oxide (Fe(2)O(3)), yttrium oxide (Y(2)O(3)), and zinc oxide (ZnO) nanoparticles and subsequently measured mRNA and protein levels of the three inflammatory markers intra-cellular cell adhesion molecule-1, interleukin-8, and monocyte chemotactic protein-1. We also determined nanoparticle interactions with HAECs using inductively coupled plasma mass spectrometry and transmission electron microscopy.
Our data indicate that nanoparticle delivery to the HAEC surface and uptake within the cells correlate directly with particle concentration in the cell culture medium. All three types of nanoparticles are internalized into HAECs and are often found within intracellular vesicles. Fe(2)O(3) nanoparticles fail to provoke an inflammatory response in HAECs at any of the concentrations tested; however, Y(2)O(3) and ZnO nanoparticles elicit a pronounced inflammatory response above a threshold concentration of 10 mug/mL. At the highest concentration, ZnO nanoparticles are cytotoxic and lead to considerable cell death.
These results demonstrate that inflammation in HAECs following acute exposure to metal oxide nanoparticles depends on particle composition.
超细颗粒暴露与心血管疾病发病率增加之间的相关机制尚不清楚。超细颗粒似乎可穿过肺上皮屏障进入血液循环，增加了与血管内皮直接接触的可能性。
由于内皮炎症对心血管病理发展至关重要，我们推测人主动脉内皮细胞（HAECs）直接暴露于超细颗粒会引发炎症反应，且该反应取决于颗粒组成。
为验证该假设，我们将HAECs与不同浓度（0.001 - 50微克/毫升）的氧化铁（Fe₂O₃）、氧化钇（Y₂O₃）和氧化锌（ZnO）纳米颗粒孵育1 - 8小时，随后测量三种炎症标志物细胞间黏附分子-1、白细胞介素-8和单核细胞趋化蛋白-1的mRNA和蛋白质水平。我们还使用电感耦合等离子体质谱和透射电子显微镜确定纳米颗粒与HAECs的相互作用。
我们的数据表明，纳米颗粒递送至HAECs表面以及在细胞内的摄取与细胞培养基中的颗粒浓度直接相关。所有三种类型的纳米颗粒均被HAECs内化，且常出现在细胞内囊泡中。在任何测试浓度下，Fe₂O₃纳米颗粒均未在HAECs中引发炎症反应；然而，Y₂O₃和ZnO纳米颗粒在阈值浓度10微克/毫升以上会引发明显的炎症反应。在最高浓度下，ZnO纳米颗粒具有细胞毒性并导致大量细胞死亡。
这些结果表明，急性暴露于金属氧化物纳米颗粒后HAECs中的炎症取决于颗粒组成。
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