The aim of the present study was to establish the mechanism of the allergy aggravation effect. Our previous study showed that soluble ZnO nanoparticles caused allergy aggravation, but insoluble TiO2 and SiO2 nanoparticles did not induce an allergic response. Metal ion release is associated with the cytotoxicity of manufactured nanoparticles; however, the role of metal ion release in allergy aggravation remains to be elucidated. Therefore, we examined the allergy aggravation potential of several soluble manufactured nanoparticles (ZnO, CuO, NiO, MgO, and CaCO3). These nanoparticles were administered to mouse lungs by pharyngeal aspiration and subsequently, the mice inhaled ovalbumin (OVA). We also compared the properties of soluble NiO nanoparticles with insoluble micro-scale NiO particles. NiO nanoparticles markedly increased the levels of OVAspecific immunoglobulin (Ig) E but micro-scale NiO particles did not. Among the nanoparticles (ZnO, CuO, MgO, and CaCO3), ZnO induced increase of OVA-specific IgE level. CuO showed tendency to increase OVA-specific IgE; however, no significant difference was observed. Additionally, ZnO and NiO nanoparticles enhanced expression of a gene related to inflammation (Cxcl2), heavy metal detox (metallothionein 2), and oxidative stress (heme oxygenase-1). Gene expression of arginase1, which is enhanced by T helper 2 cytokine, was remarkably enhanced in mice administered ZnO and NiO particles. These effects were not observed in mice administered MgO and CaCO3 nanoparticles. In conclusion, the solubility and type of metal ion released from the nanoparticles influence * Corresponding author. M. Horie et al. 18the allergy aggravation effect. The results showed that the release of Zn 2+ and Ni 2+ aggravated the allergic reaction.

The application of carbon nanotube (CNT) as a functional material to engineering and life sciences is advanced. In order to evaluate the cytotoxicity of CNT in vitro, some chemical and biological reagents are used for dispersants. In the present study, the cellular influences of six kinds of chemical or biological reagents used as dispersants were examined. Pluronic F-127, Pluronic F-68, 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC), pulmonary surfactant preparation Surfacten®, bovine serum albumin (BSA) and Tween 80 were used in the preparation of CNT-medium dispersants. The influences of each reagent on cell viability in human lung carcinoma A549 cells were small. However, Pluronic F-127, DPPC, Surfacten® and Tween 80 induced an increase of intracellular reactive oxygen species (ROS) level. Next, CNT-medium dispersions were prepared, using each reagent as a dispersant and applied to A549 cells. The cellular influences depended on the kind of dispersant. Cells exposed to CNT dispersion including Pluronic® F-127, Surfacten®, DPPC and Tween 80 showed LDH release to the culture supernatant. Induction of intracellular ROS level was observed in cells exposed to CNT dispersion including each reagent except BSA. These results suggest that the adsorbed dispersant reagents on the surface of the CNT affect its cellular influences, particularly the induction of oxidative stress.

The inhalation of manufactured metal oxide nanoparticles may lead to pulmonary toxicity. For instance, ZnO nanoparticles are known to induce pulmonary oxidative stress and inflammation. On the other hand, the pulmonary toxicity of TiO2 nanoparticles is less than that of ZnO nanoparticles. Although, there have been some investigations concerning the induction of pulmonary oxidative stress and inflammation caused by manufactured metal oxide nanoparticles. And, although, it has reported that some nanoparticles cause aggravation of allergic reactions, there have so far been no reports regarding allergy aggravation effects of manufactured metal oxide nanoparticles. In this study, three types of nanoparticles, TiO2, ZnO and SiO2, were administered to mouse lungs by pharyngeal aspiration. Subsequently, the mice inhaled ovalbumin (OVA) a total of eight times over 3 weeks. After inhalation of OVA, the concentrations of total IgE, OVA-specific IgE and OVA-specific IgG1 in serum increased in the mice treated with ZnO. TiO2 and SiO2 nanoparticles did not affect the OVA-specific IgE and IgG1 levels. These results suggest that ZnO nanoparticles have the potential to aggravate allergic reactions. The results also suggest that Zn(2+) release from ZnO nanoparticles is involved in the aggravation potential of allergies. However, pharyngeal aspiration of ZnCl2 solution was not able to aggravate allergic reactions. Continuous Zn(2+) release from ZnO nanoparticles to the lung is necessary for the aggravation of allergic reactions.

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The pulmonary toxicity of multi-wall carbon nanotubes (MWCNT) were examined by intratracheal instillation. We prepared a well-dispersed MWCNT dispersion including MWCNTs of 3.71 µm geometric average length. The fiber length of most of the MWCNTs in the dispersion was 10 µm or less. The MWCNT dispersion was administered to rat lung by single intratracheal instillation at doses of 0.2 mg and 0.6 mg/rat. Bronchoalveolar lavage fluid (BALF) was collected at 3 days, 1 week, 1 month, 3 months, and 6 months after instillation. The influences of the longer MWCNTs on the induction of inflammation and oxidative stress were examined by the number of neutrophils, cytokine induced neutrophil chemoattractant-1 (CINC-1), CINC-2, CINC-3 and HO-1 in the BALF. Additionally, ho-1 gene expression in the lung was examined. The intratracheal instillation of MWCNT induced transient inflammation dose dependently in the lung. The number of neutrophils was highest at 3 days after instillation and then decreased. However, the neutrophils in the MWCNT administered animals tended to be higher than in the control group until 3 months after instillation. The CINC-1 and CINC-2 concentrations in the BALF increased at 1 month after instillation. There were no significant differences in CINC-3 and HO-1 between the MWCNT administered animals and the control animals. These results revealed that the MWCNTs of 1–10 µm in length induced persistent inflammation in rat lung. There were no remarkable differences between the MWCNTs in the present study and previously reported, shorter MWCNTs prepared from “the same” raw MWCNT material.