Nygaard Unni C, Hansen Jitka S, Samuelsen Mari, Alberg Torunn, Marioara Calin D, Løvik Martinus
Division of Environmental Medicine, Norwegian Institute of Public Health, NO-0403 Oslo, Norway.
Toxicol Sci. 2009 May;109(1):113-23. doi: 10.1093/toxsci/kfp057. Epub 2009 Mar 17.
The adjuvant effect of particles on allergic immune responses has been shown to increase with decreasing particle size and increasing particle surface area. Like ultrafine particles, carbon nanotubes (CNTs) have nano-sized dimensions and a large relative surface area and might thus increase allergic responses. Therefore, we examined whether single-walled (sw) and multi-walled (mw) CNTs have the capacity to promote allergic responses in mice, first in an sc injection model and thereafter in an intranasal model. Balb/cA mice were exposed to three doses of swCNT, mwCNT, as well as ultrafine carbon black particles (ufCBPs, Printex90) during sensitization with the allergen ovalbumin (OVA). Five days after an OVA booster, OVA-specific IgE, IgG1, and IgG2a antibodies in serum and the numbers of inflammatory cells and cytokine levels in bronchoalveolar lavage fluid (BALF) were determined. Furthermore, ex vivo OVA-induced cytokine release from mediastinal lymph node (MLN) cells was measured. In separate experiments, differential cell counts were determined in BALF 24 h after a single intranasal exposure to the particles in the absence of allergen. We demonstrate that both swCNT and mwCNT together with OVA strongly increased serum levels of OVA-specific IgE, the number of eosinophils in BALF, and the secretion of Th2-associated cytokines in the MLN. On the other hand, only mwCNT and ufCBP with OVA increased IgG2a levels, neutrophil cell numbers, and tumor necrosis factor-alpha and monocyte chemoattractant protein-1 levels in BALF, as well as the acute influx of neutrophils after exposure to the particles alone. This study demonstrates that CNTs promote allergic responses in mice.
已表明颗粒对过敏性免疫反应的佐剂效应会随着颗粒尺寸减小和颗粒表面积增加而增强。与超细颗粒一样，碳纳米管（CNT）具有纳米尺寸且相对表面积大，因此可能会增强过敏反应。因此，我们首先在皮下注射模型中，然后在鼻内模型中研究了单壁（sw）和多壁（mw）碳纳米管是否有能力促进小鼠的过敏反应。在用变应原卵清蛋白（OVA）致敏期间，将Balb/cA小鼠暴露于三剂swCNT、mwCNT以及超细炭黑颗粒（ufCBP，Printex90）。OVA加强免疫五天后，测定血清中OVA特异性IgE、IgG1和IgG2a抗体以及支气管肺泡灌洗液（BALF）中的炎症细胞数量和细胞因子水平。此外，还测量了体外OVA诱导的纵隔淋巴结（MLN）细胞释放细胞因子的情况。在单独的实验中，在无变应原情况下单次鼻内暴露于颗粒24小时后，测定BALF中的细胞分类计数。我们证明，swCNT和mwCNT与OVA一起均强烈增加了血清中OVA特异性IgE水平、BALF中嗜酸性粒细胞数量以及MLN中Th2相关细胞因子的分泌。另一方面，只有mwCNT和ufCBP与OVA增加了BALF中的IgG2a水平、中性粒细胞数量、肿瘤坏死因子-α和单核细胞趋化蛋白-1水平，以及单独暴露于颗粒后中性粒细胞的急性流入。本研究表明碳纳米管可促进小鼠的过敏反应。
