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Cutaneous exposure to agglomerates of silica nanoparticles and allergen results in IgE-biased immune response and increased sensitivity to anaphylaxis in mice.

Hirai T, Yoshioka Y, Takahashi H, Ichihashi K, Udaka A, Mori T, Nishijima N, Yoshida T, Nagano K, Kamada H, Tsunoda S, Takagi T, Ishii KJ, Nabeshi H, Yoshikawa T, Higashisaka K, Tsutsumi Y - Part Fibre Toxicol (2015)

Bottom Line: Our data suggest that silica nanoparticles themselves do not directly affect the allergen-specific immune response after concurrent topical application of nanoparticles and allergen.However, when present in allergen-adsorbed agglomerates, silica nanoparticles led to a low IgG/IgE ratio, a key risk factor of human atopic allergies.We suggest that minimizing interactions between nanomaterials and allergens will increase the safety of nanomaterials applied to skin.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Toxicology and Safety Science, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka, 565-0871, Japan. t-hirai@phs.osaka-u.ac.jp.

ABSTRACT

Background: The skin is a key route of human exposure to nanomaterials, which typically occurs simultaneously with exposure to other chemical and environmental allergen. However, little is known about the hazards of nanomaterial exposure via the skin, particularly when accompanied by exposure to other substances.

Results: Repeated topical treatment of both ears and the shaved upper back of NC/Nga mice, which are models for human atopic dermatitis (AD), with a mixture of mite extract and silica nanoparticles induced AD-like skin lesions. Measurements of ear thickness and histologic analyses revealed that cutaneous exposure to silica nanoparticles did not aggravate AD-like skin lesions. Instead, concurrent cutaneous exposure to mite allergens and silica nanoparticles resulted in the low-level production of allergen-specific IgGs, including both the Th2-related IgG1 and Th1-related IgG2a subtypes, with few changes in allergen-specific IgE concentrations and in Th1 and Th2 immune responses. In addition, these changes in immune responses increased the sensitivity to anaphylaxis. Low-level IgG production was induced when the mice were exposed to allergen-silica nanoparticle agglomerates but not when the mice exposed to nanoparticles applied separately from the allergen or to well-dispersed nanoparticles.

Conclusions: Our data suggest that silica nanoparticles themselves do not directly affect the allergen-specific immune response after concurrent topical application of nanoparticles and allergen. However, when present in allergen-adsorbed agglomerates, silica nanoparticles led to a low IgG/IgE ratio, a key risk factor of human atopic allergies. We suggest that minimizing interactions between nanomaterials and allergens will increase the safety of nanomaterials applied to skin.

No MeSH data available.


Related in: MedlinePlus

Effect of topical application of dispersed mixture of Dp + nSP30 on antibody response. a–c Plasma levels of Dp-specific (a) IgE, (b) IgG, and (c) IgG1 and IgG2a at 24 h after final topical treatment of NC/Nga mice with Dp alone or Dp + nSP30 in water, as analyzed by ELISA. Data are given as means ± SEMs (n = 5 or 6). *P < 0.05, **P < 0.01 vs. Dp-alone group
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Fig7: Effect of topical application of dispersed mixture of Dp + nSP30 on antibody response. a–c Plasma levels of Dp-specific (a) IgE, (b) IgG, and (c) IgG1 and IgG2a at 24 h after final topical treatment of NC/Nga mice with Dp alone or Dp + nSP30 in water, as analyzed by ELISA. Data are given as means ± SEMs (n = 5 or 6). *P < 0.05, **P < 0.01 vs. Dp-alone group

Mentions: The vehicle in which nanoparticles are suspended is a key determinant of their dispersion and affects their toxicity [38, 39]. To further evaluate the effect of agglomeration of Dp and nSP30 on the IgE-biased immune response, we tested the effect of the vehicle on the formation of agglomerates and the IgE-biased immune response. Solutions of Dp and nSP30, either individually or together, in water were clear and colorless, but the combination of Dp and nSP30 in PBS was cloudy (Fig. 1a). The mean hydrodynamic diameter of nSP30 in water was 19.5 nm and that of Dp + nSP30 in water was 20.0 nm (Fig. 1c and d), indicating that mixing Dp and nSP30 in water did not cause agglomeration. We repeatedly painted NC/Nga mice with Dp + nSP30 in water and evaluated the Dp-induced antibody responses. When suspended in water, nSP30 had no effect on the level of Dp-specific IgE (Fig. 7a). In addition, the levels of Dp-specific total IgG, IgG1, and IgG2a did not differ between the Dp + nSP30 and Dp-alone groups when the vehicle used was water (Fig. 7b and c). Therefore the agglomeration of Dp and nSP30 might be necessary to impede the allergen-specific IgG response, but it did not affect the IgE response.Fig. 7


Cutaneous exposure to agglomerates of silica nanoparticles and allergen results in IgE-biased immune response and increased sensitivity to anaphylaxis in mice.

Hirai T, Yoshioka Y, Takahashi H, Ichihashi K, Udaka A, Mori T, Nishijima N, Yoshida T, Nagano K, Kamada H, Tsunoda S, Takagi T, Ishii KJ, Nabeshi H, Yoshikawa T, Higashisaka K, Tsutsumi Y - Part Fibre Toxicol (2015)

Effect of topical application of dispersed mixture of Dp + nSP30 on antibody response. a–c Plasma levels of Dp-specific (a) IgE, (b) IgG, and (c) IgG1 and IgG2a at 24 h after final topical treatment of NC/Nga mice with Dp alone or Dp + nSP30 in water, as analyzed by ELISA. Data are given as means ± SEMs (n = 5 or 6). *P < 0.05, **P < 0.01 vs. Dp-alone group
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4482284&req=5

Fig7: Effect of topical application of dispersed mixture of Dp + nSP30 on antibody response. a–c Plasma levels of Dp-specific (a) IgE, (b) IgG, and (c) IgG1 and IgG2a at 24 h after final topical treatment of NC/Nga mice with Dp alone or Dp + nSP30 in water, as analyzed by ELISA. Data are given as means ± SEMs (n = 5 or 6). *P < 0.05, **P < 0.01 vs. Dp-alone group
Mentions: The vehicle in which nanoparticles are suspended is a key determinant of their dispersion and affects their toxicity [38, 39]. To further evaluate the effect of agglomeration of Dp and nSP30 on the IgE-biased immune response, we tested the effect of the vehicle on the formation of agglomerates and the IgE-biased immune response. Solutions of Dp and nSP30, either individually or together, in water were clear and colorless, but the combination of Dp and nSP30 in PBS was cloudy (Fig. 1a). The mean hydrodynamic diameter of nSP30 in water was 19.5 nm and that of Dp + nSP30 in water was 20.0 nm (Fig. 1c and d), indicating that mixing Dp and nSP30 in water did not cause agglomeration. We repeatedly painted NC/Nga mice with Dp + nSP30 in water and evaluated the Dp-induced antibody responses. When suspended in water, nSP30 had no effect on the level of Dp-specific IgE (Fig. 7a). In addition, the levels of Dp-specific total IgG, IgG1, and IgG2a did not differ between the Dp + nSP30 and Dp-alone groups when the vehicle used was water (Fig. 7b and c). Therefore the agglomeration of Dp and nSP30 might be necessary to impede the allergen-specific IgG response, but it did not affect the IgE response.Fig. 7

Bottom Line: Our data suggest that silica nanoparticles themselves do not directly affect the allergen-specific immune response after concurrent topical application of nanoparticles and allergen.However, when present in allergen-adsorbed agglomerates, silica nanoparticles led to a low IgG/IgE ratio, a key risk factor of human atopic allergies.We suggest that minimizing interactions between nanomaterials and allergens will increase the safety of nanomaterials applied to skin.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Toxicology and Safety Science, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka, 565-0871, Japan. t-hirai@phs.osaka-u.ac.jp.

ABSTRACT

Background: The skin is a key route of human exposure to nanomaterials, which typically occurs simultaneously with exposure to other chemical and environmental allergen. However, little is known about the hazards of nanomaterial exposure via the skin, particularly when accompanied by exposure to other substances.

Results: Repeated topical treatment of both ears and the shaved upper back of NC/Nga mice, which are models for human atopic dermatitis (AD), with a mixture of mite extract and silica nanoparticles induced AD-like skin lesions. Measurements of ear thickness and histologic analyses revealed that cutaneous exposure to silica nanoparticles did not aggravate AD-like skin lesions. Instead, concurrent cutaneous exposure to mite allergens and silica nanoparticles resulted in the low-level production of allergen-specific IgGs, including both the Th2-related IgG1 and Th1-related IgG2a subtypes, with few changes in allergen-specific IgE concentrations and in Th1 and Th2 immune responses. In addition, these changes in immune responses increased the sensitivity to anaphylaxis. Low-level IgG production was induced when the mice were exposed to allergen-silica nanoparticle agglomerates but not when the mice exposed to nanoparticles applied separately from the allergen or to well-dispersed nanoparticles.

Conclusions: Our data suggest that silica nanoparticles themselves do not directly affect the allergen-specific immune response after concurrent topical application of nanoparticles and allergen. However, when present in allergen-adsorbed agglomerates, silica nanoparticles led to a low IgG/IgE ratio, a key risk factor of human atopic allergies. We suggest that minimizing interactions between nanomaterials and allergens will increase the safety of nanomaterials applied to skin.

No MeSH data available.


Related in: MedlinePlus