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细菌来源的纳米大小外膜囊泡的体内动力学生物分布。

In vivo kinetic biodistribution of nano-sized outer membrane vesicles derived from bacteria.

机构信息

Department of Life Sciences, Pohang University of Science and Technology, Pohang, 790-784, Republic of Korea.

出版信息

Small. 2015 Jan 27;11(4):456-61. doi: 10.1002/smll.201401803. Epub 2014 Sep 5.

DOI:10.1002/smll.201401803
PMID:25196673
Abstract

Evaluation of kinetic distribution and behaviors of nanoparticles in vivo provides crucial clues into their roles in living organisms. Extracellular vesicles are evolutionary conserved nanoparticles, known to play important biological functions in intercellular, inter-species, and inter-kingdom communication. In this study, the first kinetic analysis of the biodistribution of outer membrane vesicles (OMVs)-bacterial extracellular vesicles-with immune-modulatory functions is performed. OMVs, injected intraperitoneally, spread to the whole mouse body and accumulate in the liver, lung, spleen, and kidney within 3 h of administration. As an early systemic inflammation response, increased levels of TNF-α and IL-6 are observed in serum and bronchoalveolar lavage fluid. In addition, the number of leukocytes and platelets in the blood is decreased. OMVs and cytokine concentrations, as well as body temperature are gradually decreased 6 h after OMV injection, in concomitance with the formation of eye exudates, and of an increase in ICAM-1 levels in the lung. Following OMV elimination, most of the inflammatory signs are reverted, 12 h post-injection. However, leukocytes in bronchoalveolar lavage fluid are increased as a late reaction. Taken together, these results suggest that OMVs are effective mediators of long distance communication in vivo.

摘要

评价纳米颗粒在体内的动力学分布和行为为其在生物体内的作用提供了重要线索。细胞外囊泡是进化保守的纳米颗粒,已知在细胞间、种间和种属间的通讯中发挥着重要的生物学功能。在这项研究中,首次对具有免疫调节功能的外膜囊泡(OMV)-细菌细胞外囊泡的生物分布进行了动力学分析。OMV 经腹腔注射后,在给药 3 小时内扩散到小鼠全身,并在肝脏、肺、脾和肾脏中积累。作为早期的全身炎症反应,血清和支气管肺泡灌洗液中 TNF-α和 IL-6 的水平升高。此外,血液中的白细胞和血小板数量减少。OMV 和细胞因子浓度以及体温在 OMV 注射后 6 小时逐渐下降,同时出现眼睛分泌物和肺中 ICAM-1 水平升高。在 OMV 消除后,注射后 12 小时,大多数炎症迹象得到逆转。然而,支气管肺泡灌洗液中的白细胞增加是一种迟发反应。综上所述,这些结果表明 OMV 是体内长距离通讯的有效介质。

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