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在胎儿发育中后期暴露于炭黑纳米颗粒会诱导雄性后代小鼠的免疫激活。

Carbon black nanoparticle exposure during middle and late fetal development induces immune activation in male offspring mice.

作者信息

El-Sayed Yasser S, Shimizu Ryuhei, Onoda Atsuto, 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, 2641 Yamazaki, Noda, Chiba 278-8510, Japan; Department of Veterinary Forensic Medicine and Toxicology, Faculty of Veterinary Medicine, Damanhour University, Damanhour 22511, Egypt.

Department of Hygienic Chemistry, Graduate School of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba 278-8510, Japan.

出版信息

Toxicology. 2015 Jan 2;327:53-61. doi: 10.1016/j.tox.2014.11.005. Epub 2014 Nov 22.

Abstract

Increasing exposure to nanoparticles (NPs) has raised concerns regarding their health and safety profiles in humans and animals, especially in developing organisms, which may display increased sensitivity to NP toxicity. The present study examined the effects of gestational exposure to carbon black NP (CB-NP) on the development of the offspring immune system. Pregnant mice were exposed to CB-NP (95μg/kg body weight) by intranasal instillation on gestational days 9 and 15. The thymus and spleen were collected from their offspring mice on postnatal day (PND) 1, 3 and 5. Thymocyte and splenocyte phenotypes were examined by determining the expression of cell-surface molecules using flow cytometry. Gene expression in the thymus and spleen was examined using quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Prenatal exposure to CB-NP increased total thymocytes and their immunophenotypes (CD4(-)CD8(-) and CD4(+)CD8(+) cells). It also induced an increase in total lymphocytes, and CD4(-)CD8(-), particularly CD3(-)B220(-)cells, at PND 5 in the spleen of newborn male offspring, reflecting the stimulation of immature splenocytes. Furthermore, mRNA expression of genes related to the induction of peripheral tolerance (i.e. thymic Traf6) was upregulated. These data suggest that respiratory exposure to CB-NP during middle and late gestation may have allergic or inflammatory effects in male offspring, and may provide initial information on the potential developmental immunotoxicity of nanoparticles.

摘要

越来越多地接触纳米颗粒(NPs)引发了人们对其在人类和动物,尤其是发育中的生物体中的健康和安全状况的担忧,因为这些生物体可能对NP毒性表现出更高的敏感性。本研究考察了孕期接触炭黑纳米颗粒(CB-NP)对后代免疫系统发育的影响。在妊娠第9天和第15天,通过滴鼻法让怀孕小鼠接触CB-NP(95μg/kg体重)。在出生后第1天、第3天和第5天从它们的后代小鼠身上采集胸腺和脾脏。通过流式细胞术测定细胞表面分子的表达来检测胸腺细胞和脾细胞的表型。使用定量逆转录-聚合酶链反应(qRT-PCR)检测胸腺和脾脏中的基因表达。产前接触CB-NP增加了胸腺细胞总数及其免疫表型(CD4(-)CD8(-)和CD4(+)CD8(+)细胞)。它还导致新生雄性后代脾脏中总淋巴细胞以及CD4(-)CD8(-)细胞,特别是CD3(-)B220(-)细胞在出生后第5天增加,这反映了未成熟脾细胞受到刺激。此外,与外周耐受诱导相关的基因(即胸腺Traf6)的mRNA表达上调。这些数据表明,在妊娠中期和晚期经呼吸道接触CB-NP可能对雄性后代产生过敏或炎症影响,并可能为纳米颗粒潜在的发育免疫毒性提供初步信息。

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