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炭黑纳米颗粒对新生小鼠淋巴组织的影响:取决于小鼠孕期暴露情况

Effect of Carbon Black Nanoparticle on Neonatal Lymphoid Tissues Depending on the Gestational Period of Exposure in Mice.

作者信息

Onoda Atsuto, Okamoto Saki, Shimizu Ryuhei, El-Sayed Yasser S, Watanabe Shiho, Ogawa Shuhei, Abe Ryo, Kamimura Masao, Soga Kohei, Tachibana Ken, Takeda Ken, Umezawa Masakazu

机构信息

The Center for Environmental Health Science for the Next Generation, Research Institute for Science and Technology, Tokyo University of Science, Noda, Japan.

Faculty of Pharmaceutical Sciences, Tokyo University of Science, Noda, Japan.

出版信息

Front Toxicol. 2021 Aug 11;3:700392. doi: 10.3389/ftox.2021.700392. eCollection 2021.

Abstract

Particulate air pollution, containing nanoparticles, enhances the risk of pediatric allergic diseases that is potentially associated with disruption of neonatal immune system. Previous studies have revealed that maternal exposure to carbon black nanoparticles (CB-NP) disturbs the development of the lymphoid tissues in newborns. Interestingly, the CB-NP-induced immune profiles were observed to be different depending on the gestational period of exposure. It is important to identify the critical exposure period to prevent toxic effects of nanoparticles on the development of the immune system. Therefore, the present study was aimed to investigate the effect of CB-NP on the development of neonatal lymphoid tissues in mice, depending on the gestational period of exposure. Pregnant ICR mice were treated with a suspension of CB-NP (95 μg/kg body weight) by intranasal instillation; the suspension was administered twice during each gestational period as follows: the pre-implantation period (gestational days 4 and 5), organogenesis period (gestational days 8 and 9), and fetal developmental period (gestational days 15 and 16). The spleen and thymus were collected from offspring mice at 1, 3, and 5-days post-partum. Splenocyte and thymocyte phenotypes were examined by flow cytometry. Gene expression in the spleen was examined by quantitative reverse transcription-polymerase chain reaction. The numbers of total splenocytes and splenic CD3B220 phenotype (non-T/non-B lymphocytes) in offspring on postnatal day 5 were significantly increased after exposure to CB-NP during the organogenesis period compared with other gestational periods of exposure and control (no exposure). In contrast, expression levels of mRNA associated with chemotaxis and differentiation of immune cells in the spleen were not affected by CB-NP exposure during any gestational period. The organogenesis period was the most susceptible period to CB-NP exposure with respect to lymphoid tissue development. Moreover, the findings of the present and previous studies suggested that long-term exposure to CB-NP across multiple gestational periods including the organogenesis period, rather than acute exposure only organogenesis period, may more severely affect the development of the immune system.

摘要

含有纳米颗粒的空气颗粒物污染会增加儿童过敏性疾病的风险,这可能与新生儿免疫系统紊乱有关。先前的研究表明,母体暴露于炭黑纳米颗粒(CB-NP)会干扰新生儿淋巴组织的发育。有趣的是,观察到CB-NP诱导的免疫谱因暴露的妊娠期而异。确定关键暴露期对于预防纳米颗粒对免疫系统发育的毒性作用很重要。因此,本研究旨在探讨CB-NP对小鼠新生儿淋巴组织发育的影响,具体取决于暴露的妊娠期。将怀孕的ICR小鼠通过滴鼻法给予CB-NP悬浮液(95μg/kg体重);在每个妊娠期分两次给予悬浮液,具体如下:着床前期(妊娠第4天和第5天)、器官形成期(妊娠第8天和第9天)和胎儿发育期(妊娠第15天和第16天)。在产后1天、3天和5天从后代小鼠中收集脾脏和胸腺。通过流式细胞术检测脾细胞和胸腺细胞表型。通过定量逆转录-聚合酶链反应检测脾脏中的基因表达。与其他暴露妊娠期和对照组(未暴露)相比,在器官形成期暴露于CB-NP后,出生后第5天后代中的总脾细胞数量和脾脏CD3B220表型(非T/非B淋巴细胞)显著增加。相比之下,在任何妊娠期,CB-NP暴露均未影响脾脏中与免疫细胞趋化和分化相关的mRNA表达水平。就淋巴组织发育而言,器官形成期是对CB-NP暴露最敏感的时期。此外,本研究和先前研究的结果表明,在包括器官形成期在内的多个妊娠期长期暴露于CB-NP,而不是仅在器官形成期急性暴露,可能会更严重地影响免疫系统的发育。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5bad/8915855/d69f11697644/ftox-03-700392-g001.jpg

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