Orr Galya, Panther David J, Phillips Jaclyn L, Tarasevich Barbara J, Dohnalkova Alice, Hu Dehong, Teeguarden Justin G, Pounds Joel G
Chemical and Materials Sciences, Pacific Northwest National Laboratory, Richland, Washington 99354, USA.
ACS Nano. 2007 Dec;1(5):463-75. doi: 10.1021/nn700149r.
The growing commerce in micro- and nanotechnology is expected to increase human exposure to submicrometer and nanoscale particles, including certain forms of amorphous silica. When inhaled, these particles are likely to reach the alveoli, where alveolar type II epithelial cells that are distinguished by apical microvilli are found. These cells play critical roles in the function of the alveoli and participate in the immune response to amorphous silica and other particles by releasing chemokines. The cellular interactions of the particles, which drive the cellular responses, are still unclear. Adverse effects of nanoparticles have been attributed, in part, to the unique properties of materials at the nanoscale. However, little is known about the cellular interactions of individual or small nanoparticle aggregates, mostly because of their tendency to agglomerate under experimental conditions. Here we investigate the interaction and internalization pathway of individual precipitated amorphous silica particles with specific surface properties and size, by following one particle at a time. We find that both 100 and 500 nm particles can take advantage of the actin turnover machinery within filopodia and microvilli-like structures to advance their way into alveolar type II epithelial cells. This pathway is strictly dependent on the positive surface charge of the particle and on the integrity of the actin filaments, unraveling the coupling of the particle with the intracellular environment across the cell membrane. The retrograde pathway brings a new mechanism by which positive surface charge supports particle recruitment, and potential subsequent toxicity, by polarized epithelial cells bearing microvilli.
微米和纳米技术领域不断增长的商业活动预计会增加人类接触亚微米和纳米级颗粒的机会，其中包括某些形式的无定形二氧化硅。吸入这些颗粒后，它们很可能会到达肺泡，在那里可以发现具有顶端微绒毛的II型肺泡上皮细胞。这些细胞在肺泡功能中发挥着关键作用，并通过释放趋化因子参与对无定形二氧化硅和其他颗粒的免疫反应。驱动细胞反应的颗粒与细胞之间的相互作用仍不清楚。纳米颗粒的不良影响部分归因于纳米级材料的独特性质。然而，对于单个或小的纳米颗粒聚集体的细胞相互作用知之甚少，主要是因为它们在实验条件下容易团聚。在这里，我们通过一次追踪一个颗粒，研究具有特定表面性质和尺寸的单个沉淀无定形二氧化硅颗粒的相互作用和内化途径。我们发现，100纳米和500纳米的颗粒都可以利用丝状伪足和微绒毛样结构内的肌动蛋白周转机制进入II型肺泡上皮细胞。这条途径严格依赖于颗粒的正表面电荷和肌动蛋白丝的完整性，揭示了颗粒通过细胞膜与细胞内环境的耦合。逆行途径带来了一种新机制，即正表面电荷通过带有微绒毛的极化上皮细胞支持颗粒募集以及潜在的后续毒性。
