Ultrafine particles cross cellular membranes by nonphagocytic mechanisms in lungs and in cultured cells.
Ultrafine particles cross cellular membranes by nonphagocytic mechanisms in lungs and in cultured cells.
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DOI：
10.1289/ehp.8006
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发表时间：
2005-11
影响因子：
10.4
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中科院分区：
文献类型：
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高浓度的空气颗粒物与肺和心血管死亡率增加有关，有迹象表明超细颗粒物（UFP;颗粒< 0.1 μm）具有特定的毒理作用。呼吸系统暴露于UFP后数小时内，UFP可能出现在身体的许多隔室中，包括肝脏，心脏和神经系统。迄今为止，UFP穿透边界膜的机制以及UFP在其主要和次要靶器官的组织隔室中的分布在很大程度上是未知的。我们结合不同的实验方法来研究UFP在肺中的分布及其被细胞摄取。在体内实验中，大鼠吸入计数中值直径为22 nm的超细二氧化钛气溶胶。在暴露结束后1小时或24小时，使用能量过滤透射电子显微镜对单个颗粒进行元素微量分析，分析颗粒的肺内分布。在体外研究中，我们将肺巨噬细胞和红细胞暴露于荧光聚苯乙烯微球（1、0.2和0.078 μm），并通过共聚焦激光扫描显微镜评估颗粒摄取。在气道和肺泡的腔侧、所有主要肺组织隔室和细胞以及毛细血管内发现吸入的超细二氧化钛颗粒。在体外细胞中的颗粒摄取没有发生任何预期的内吞过程，而是通过扩散或粘附相互作用。细胞内的颗粒不是膜结合的，因此可以直接接触细胞内的蛋白质、细胞器和DNA，这可能会大大增强它们的毒性潜力。
High concentrations of airborne particles have been associated with increased pulmonary and cardiovascular mortality, with indications of a specific toxicologic role for ultrafine particles (UFPs; particles < 0.1 μm). Within hours after the respiratory system is exposed to UFPs, the UFPs may appear in many compartments of the body, including the liver, heart, and nervous system. To date, the mechanisms by which UFPs penetrate boundary membranes and the distribution of UFPs within tissue compartments of their primary and secondary target organs are largely unknown. We combined different experimental approaches to study the distribution of UFPs in lungs and their uptake by cells. In the in vivo experiments, rats inhaled an ultrafine titanium dioxide aerosol of 22 nm count median diameter. The intrapulmonary distribution of particles was analyzed 1 hr or 24 hr after the end of exposure, using energy-filtering transmission electron microscopy for elemental microanalysis of individual particles. In an in vitro study, we exposed pulmonary macrophages and red blood cells to fluorescent polystyrene microspheres (1, 0.2, and 0.078 μm) and assessed particle uptake by confocal laser scanning microscopy. Inhaled ultrafine titanium dioxide particles were found on the luminal side of airways and alveoli, in all major lung tissue compartments and cells, and within capillaries. Particle uptake in vitro into cells did not occur by any of the expected endocytic processes, but rather by diffusion or adhesive interactions. Particles within cells are not membrane bound and hence have direct access to intracellular proteins, organelles, and DNA, which may greatly enhance their toxic potential.