Differences in the biokinetics of inhaled nano- versus micrometer-sized particles.
Differences in the biokinetics of inhaled nano- versus micrometer-sized particles.
复制标题
DOI：
10.1021/ar300043r
复制
发表时间：
2013-03-19
影响因子：
18.3
通讯作者：
Moeller, Winfried
中科院分区：
文献类型：
--
作者：
Kreyling, Wolfgang G.;Semmler-Behnke, Manuela;Takenaka, Shinji;Moeller, Winfried
研究人员需要研究吸入的生物持久性纳米和微米尺寸颗粒（NP 和 μP）的生物动力学，以评估其毒性并了解其潜在风险。当颗粒被吸入时，它们不一定保留在呼吸道中的沉积部位。相反，它们可以在肺部的各种组织内经历许多运输过程，包括从肺部清除。在这种情况下，我们想了解如何将在动物身上进行的生物动力学研究外推到人类。有趣的是，啮齿类动物肺部的颗粒滞留时间比人类、猿猴和犬类肺部的颗粒滞留时间短得多，下降速度也快得多。人类和其他动物物种中 NP 和 μP 的主要长期清除途径是巨噬细胞介导的颗粒从周围肺向纤毛气道和喉的转运。然而，啮齿类动物的转运率比其他物种高 10 倍。除了从肺部清除颗粒之外，我们还观察到颗粒从上皮向肺间质和淋巴结及其内部重新分布，以及颗粒易位到血液循环，导致随后在次要器官中积累。虽然 μP 进入啮齿动物肺间质空间的能力有限，但 NP 会迅速重新定位在上皮和下面的间质中。相比之下，间接证据表明，NP 和 μP 均重新定位到人类、猿猴和犬肺的上皮和间质空间中。只有 NP 易位到循环系统中，随后在身体的次要器官和组织中积累。易位的纳米粒子分数相当低，但它们很大程度上取决于纳米粒子的物理化学性质及其表面性质。越来越多的证据表明，蛋白质与纳米颗粒的结合和缀合在穿过细胞膜和器官屏障的易位中发挥着重要作用。总之，颗粒生物动力学是由众多高度动态的过程产生的，这些过程不仅取决于颗粒的物理化学性质，还取决于大量的细胞和分子反应和相互作用。鉴于急性吸入暴露后次要器官中的积累量相当小，看来次要器官中积累的纳米粒子引起的不利影响可能只有在长期慢性暴露后才会发生。因此，与长期暴露于城市周围空气污染相关的次要器官（例如心血管系统）的不良健康影响不太可能是由颗粒易位造成的。相反，长期吸入颗粒可能会触发或调节自主神经系统或将可溶性介质释放到循环中，从而对健康产生不利影响。
Researchers need to study the biokinetics of inhaled biopersistent nano- and micrometer-sized particles (NPs and μPs) to assess their toxicity and to develop an understanding of their potential risks. When particles are inhaled, they do not necessarily remain at their sites of deposition in the respiratory tract. Instead they can undergo numerous transport processes within the various tissues of the lungs, including clearance from the lungs. In this context, we would like to understand how the biokinetic studies performed in animals can be extrapolated to humans. Interestingly, the particle retention is much shorter in rodent lungs and declines much faster than it does in human, simian, and canine lungs.The predominant long-term clearance pathway for both NPs and μPs in humans and other animal species is macrophage-mediated particle transport from the peripheral lungs toward ciliated airways and the larynx. However, the transport rate is 10 times higher in rodents than in other species. In addition to particle clearance out of the lung, we also observe particle redistribution from the epithelium toward and within the interstitium and lymph nodes of the lung and particle translocation to blood circulation leading to subsequent accumulation in secondary organs. While μPs have limited access to interstitial spaces in the rodent lungs, NPs rapidly relocate in the epithelium and the underlying interstitium. By contrast, indirect evidence shows that both NPs and μPs are relocated into the epithelium and interstitial spaces of the human, simian, and canine lungs.Only NPs translocate into the circulatory system and subsequently accumulate in the secondary organs and tissues of the body. Translocated NP fractions are rather low, but they depend strongly on the physicochemical properties of the NP and their surface properties. Growing evidence indicates that the binding and conjugation of proteins to NPs play an essential role in translocation across cellular membranes and organ barriers.In summary, particle biokinetics result from a multitude of highly dynamic processes, which depend not only on physicochemical properties of the particles but also on a multitude of cellular and molecular responses and interactions. Given the rather small accumulation in secondary organs after acute inhalation exposures, it appears likely that adverse effects caused by NPs accumulated in secondary organs may only occur after chronic exposure over extended time periods. Therefore adverse health effects in secondary organs such as the cardiovascular system that are associated with chronic exposure of ambient urban air pollution are less likely to result from particle translocation. Instead, chronic particle inhalation could trigger or modulate the autonomous nervous system or the release of soluble mediators into circulation leading to adverse health effects.
登录
查看更多内容
影响因子：
3.3
作者：
Kreyling, WG;Blanchard, JD;Ziesenis, A
通讯作者：
Ziesenis, A
影响因子：
--
作者：
OBERDORSTER, G
通讯作者：
OBERDORSTER, G
影响因子：
10.4
作者：
通讯作者：
--
影响因子：
10.4
作者：
ELLENDER, M;HODGSON, A;MOODY, JC
通讯作者：
MOODY, JC
DOI：
10.1165/ajrcmb/1.2.145
发表时间：
1989-08-01
影响因子：
6.4
作者：
LEHNERT, BE;VALDEZ, YE;TIETJEN, GL
通讯作者：
TIETJEN, GL