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初级肺上皮细胞内化多分散碳纳米管后增殖和抗原呈递活性丧失。

Loss of proliferation and antigen presentation activity following internalization of polydispersed carbon nanotubes by primary lung epithelial cells.

机构信息

School of Life Sciences, Jawaharlal Nehru University, New Delhi India.

出版信息

PLoS One. 2012;7(2):e31890. doi: 10.1371/journal.pone.0031890. Epub 2012 Feb 27.

Abstract

Interactions between poly-dispersed acid functionalized single walled carbon nanotubes (AF-SWCNTs) and primary lung epithelial (PLE) cells were studied. Peritoneal macrophages (PMs, known phagocytic cells) were used as positive controls in this study. Recovery of live cells from cultures of PLE cells and PMs was significantly reduced in the presence of AF-SWCNTs, in a time and dose dependent manner. Both PLE cells as well as PMs could take up fluorescence tagged AF-SWCNTs in a time dependent manner and this uptake was significantly blocked by cytochalasin D, an agent that blocks the activity of acto-myosin fibers and therefore the phagocytic activity of cells. Confocal microscopic studies confirmed that AF-SWCNTs were internalized by both PLE cells and PMs. Intra-trachially instilled AF-SWCNTs could also be taken up by lung epithelial cells as well as alveolar macrophages. Freshly isolated PLE cells had significant cell division activity and cell cycling studies indicated that treatment with AF-SWCNTs resulted in a marked reduction in S-phase of the cell cycle. In a previously standardized system to study BCG antigen presentation by PLE cells and PMs to sensitized T helper cells, AF-SWCNTs could significantly lower the antigen presentation ability of both cell types. These results show that mouse primary lung epithelial cells can efficiently internalize AF-SWCNTs and the uptake of nanotubes interfered with biological functions of PLE cells including their ability to present BCG antigens to sensitized T helper cells.

摘要

研究了多分散酸功能化单壁碳纳米管(AF-SWCNT)与原代肺上皮(PLE)细胞之间的相互作用。在这项研究中,腹膜巨噬细胞(PM,已知的吞噬细胞)被用作阳性对照。在 AF-SWCNT 的存在下,PLE 细胞和 PM 培养物中活细胞的回收明显减少,呈时间和剂量依赖性。PLE 细胞和 PM 都可以在时间依赖性的方式摄取荧光标记的 AF-SWCNT,并且细胞松弛素 D 显著阻断了这种摄取,细胞松弛素 D 是一种阻断肌动球蛋白纤维活性的药物,因此也阻断了细胞的吞噬活性。共焦显微镜研究证实,AF-SWCNT 被 PLE 细胞和 PM 内化。经气管内滴注的 AF-SWCNT 也可被肺上皮细胞和肺泡巨噬细胞摄取。新鲜分离的 PLE 细胞具有显著的细胞分裂活性,细胞周期研究表明,AF-SWCNT 的处理导致细胞周期 S 期明显减少。在研究 PLE 细胞和 PM 向致敏 T 辅助细胞呈递 BCG 抗原的标准化系统中,AF-SWCNT 可显著降低两种细胞类型的抗原呈递能力。这些结果表明,小鼠原代肺上皮细胞可以有效地内化 AF-SWCNT,并且纳米管的摄取干扰了 PLE 细胞的生物学功能,包括其向致敏 T 辅助细胞呈递 BCG 抗原的能力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e570/3287983/5dbdf020803a/pone.0031890.g001.jpg

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