Pulmonary and systemic immune response to inhaled multiwalled carbon nanotubes

Pulmonary and systemic immune response to inhaled multiwalled carbon nanotubes
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DOI:
10.1093/toxsci/kfm196
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发表时间:
2007-11-01
影响因子:
3.8
通讯作者:
McDonald, Jacob D.
McDonald, Jacob D.
中科院分区:
医学2区
文献类型:
--
作者:
Mitchell, Leah A.;Gao, Jun;McDonald, Jacob D.

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吸入颗粒浓度为0.3至5 mg/m3的多壁碳纳米管(MWCNTs)不会导致显著的肺部炎症或组织损伤,但会导致全身免疫功能改变。C57 BL/6成年(10至12周)雄性小鼠通过全身吸入暴露于对照空气或0.3、1或5 mg/m3(3)可吸入多壁碳纳米管聚集体7或14天(6小时/天)。暴露动物的肺组织病理学显示肺泡巨噬细胞含有黑色颗粒;但未观察到炎症或组织损伤。支气管肺泡灌洗液也显示出充满颗粒的巨噬细胞;然而,与对照组相比,白色血细胞计数未增加。多壁碳纳米管暴露于0.3 mg/m3和更高的颗粒浓度导致非单调的全身免疫抑制后14天,但不是7天后。免疫抑制的特征是在存在有丝分裂原伴刀豆球蛋白A的情况下,对绵羊红细胞的T细胞依赖性抗体应答以及T细胞增殖能力降低。对非特异性自然杀伤(NK)细胞活性的评估表明,接触1 mg/m3的动物NK细胞功能下降。在肺组织和脾中评估所选细胞因子和氧化应激指标的基因表达分析。在肺中未观察到基因表达的变化;然而,脾中白细胞介素-10(IL-10)和NAD(P)H氧化还原酶1 mRNA水平升高。
Inhalation of multiwalled carbon nanotubes (MWCNTs) at particle concentrations ranging from 0.3 to 5 mg/m(3) did not result in significant lung inflammation or tissue damage, but caused systemic immune function alterations. C57BL/6 adult (10- to 12-week) male mice were exposed by whole-body inhalation to control air or 0.3, 1, or 5 mg/m(3) respirable aggregates of MWCNTs for 7 or 14 days (6 h/day). Histopathology of lungs from exposed animals showed alveolar macrophages containing black particles; however, there was no inflammation or tissue damage observed. Bronchial alveolar lavage fluid also demonstrated particle-laden macrophages; however, white blood cell counts were not increased compared to controls. MWCNT exposures to 0.3 mg/m(3) and higher particle concentrations caused nonmonotonic systemic immunosuppression after 14 days but not after 7 days. Immunosuppression was characterized by reduced T-cell-dependent antibody response to sheep erythrocytes as well as T-cell proliferative ability in presence of mitogen, Concanavalin A. Assessment of nonspecific natural killer (NK) cell activity showed that animals exposed to 1 mg/m(3) had decreased NK cell function. Gene expression analysis of selected cytokines and an indicator of oxidative stress were assessed in lung tissue and spleen. No changes in gene expression were observed in lung; however, interleukin-10 (IL-10) and NAD(P)H oxidoreductase 1 mRNA levels were increased in spleen.