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吸入可溶性铅纳米颗粒后清除期并未减轻免疫应答下降对靶组织的负面影响。

A Clearance Period after Soluble Lead Nanoparticle Inhalation Did Not Ameliorate the Negative Effects on Target Tissues Due to Decreased Immune Response.

机构信息

Department of Histology and Embryology, Faculty of Medicine, Masaryk University, 625 00 Brno, Czech Republic.

Laboratory of Molecular Morphogenesis, Institute of Animal Physiology and Genetics, v.v.i., Czech Academy of Sciences, 602 00 Brno, Czech Republic.

出版信息

Int J Mol Sci. 2020 Nov 19;21(22):8738. doi: 10.3390/ijms21228738.

DOI:10.3390/ijms21228738
PMID:33228049
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7699374/
Abstract

The inhalation of metal (including lead) nanoparticles poses a real health issue to people and animals living in polluted and/or industrial areas. In this study, we exposed mice to lead(II) nitrate nanoparticles [Pb(NO) NPs], which represent a highly soluble form of lead, by inhalation. We aimed to uncover the effects of their exposure on individual target organs and to reveal potential variability in the lead clearance. We examined (i) lead biodistribution in target organs using laser ablation and inductively coupled plasma mass spectrometry (LA-ICP-MS) and atomic absorption spectrometry (AAS), (ii) lead effect on histopathological changes and immune cells response in secondary target organs and (iii) the clearance ability of target organs. In the lungs and liver, Pb(NO) NP inhalation induced serious structural changes and their damage was present even after a 5-week clearance period despite the lead having been almost completely eliminated from the tissues. The numbers of macrophages significantly decreased after 11-week Pb(NO) NP inhalation; conversely, abundance of alpha-smooth muscle actin (α-SMA)-positive cells, which are responsible for augmented collagen production, increased in both tissues. Moreover, the expression of nuclear factor κB () and selected cytokines, such as tumor necrosis factor alpha (), transforming growth factor beta 1 (), interleukin 6(), and , displayed a tissue-specific response to lead exposure. In summary, diminished inflammatory response in tissues after Pb(NO) NPs inhalation was associated with prolonged negative effect of lead on tissues, as demonstrated by sustained pathological changes in target organs, even after long clearance period.

摘要

吸入金属(包括铅)纳米颗粒会对生活在污染和/或工业区的人和动物的健康造成真正的问题。在这项研究中,我们通过吸入使小鼠暴露于硝酸铅(II)纳米颗粒 [Pb(NO) NPs],这是一种具有高可溶性的铅形式。我们旨在揭示其暴露对个别靶器官的影响,并揭示潜在的铅清除能力的变异性。我们检查了 (i) 使用激光烧蚀和电感耦合等离子体质谱 (LA-ICP-MS) 和原子吸收光谱 (AAS) 检测靶器官中的铅生物分布,(ii) 铅对次级靶器官的组织病理学变化和免疫细胞反应的影响,以及 (iii) 靶器官的清除能力。在肺部和肝脏中,Pb(NO) NP 吸入引起了严重的结构变化,尽管组织中的铅几乎已完全清除,但在 5 周的清除期后仍存在其损伤。在 11 周的 Pb(NO) NP 吸入后,巨噬细胞数量显著减少;相反,α-平滑肌肌动蛋白 (α-SMA) 阳性细胞的丰度在两种组织中均增加,这些细胞负责增加胶原蛋白的产生。此外,核因子 κB () 和选定细胞因子(如肿瘤坏死因子α ()、转化生长因子β 1 ( )、白细胞介素 6 ()、和 )的表达对铅暴露表现出组织特异性反应。总之,在 Pb(NO) NPs 吸入后组织中炎症反应减弱与铅对组织的持续负面影响有关,即使在长时间的清除期后,靶器官的持续病理变化也证明了这一点。

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