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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

Effects of Dp + nSP30 aggregates compared with Dp and nSP30 administered on alternate days. a Effect of topical application of Dp + nSP30 and PBS (Dp + nSP30/PBS) compared with Dp and nSP30 (Dp/nSP30) on alternate days on ear thickness in NC/Nga mice. b–e Plasma levels of (b) total IgE, (c) Dp-specific IgE, (d) IgG and (e) IgG1 and IgG2a 24 h after final treatment, as analyzed by ELISA. f Numbers of Dp-specific IFN-γ- and IL-4-producing splenocytes after re-stimulation with 100 μg mL−1 Dp, as determined by ELISPOT assays specific for each cytokine. Data are presented as means ± SEMs (n = 5). *P < 0.05, **P < 0.01 vs. Dp/PBS group
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Fig5: Effects of Dp + nSP30 aggregates compared with Dp and nSP30 administered on alternate days. a Effect of topical application of Dp + nSP30 and PBS (Dp + nSP30/PBS) compared with Dp and nSP30 (Dp/nSP30) on alternate days on ear thickness in NC/Nga mice. b–e Plasma levels of (b) total IgE, (c) Dp-specific IgE, (d) IgG and (e) IgG1 and IgG2a 24 h after final treatment, as analyzed by ELISA. f Numbers of Dp-specific IFN-γ- and IL-4-producing splenocytes after re-stimulation with 100 μg mL−1 Dp, as determined by ELISPOT assays specific for each cytokine. Data are presented as means ± SEMs (n = 5). *P < 0.05, **P < 0.01 vs. Dp/PBS group

Mentions: We also evaluated the effects of sequential (rather than concurrent) cutaneous exposure to Dp and nSP30; that is, we topically applied Dp and nSP30 on alternate days rather than applying them together on the same day. Ear thickening and changes in total IgE concentration resulting from alternate-day application of Dp and nSP30 (Dp/nSP30) did not differ significantly from those resulting from concurrent treatment with Dp and PBS every other day (Dp/PBS) (Fig. 5a and b). Taken together, our results indicate that cutaneous exposure to nSP30 did not aggravate Dp-induced AD-like skin lesions regardless of whether the nanoparticles were applied together with or separately from Dp. In addition, alternate-day skin painting with Dp and nSP30 induced Dp-specific IgE and IgG production and Dp-specific IFN-γ- and IL-4-secreting splenocytes in the same way as did topical application of Dp and PBS (Fig. 5c–f). Therefore, exposure to both Dp and nSP30 was necessary to induce an IgE-biased immune response. Given that Dp + nSP30 formed agglomerates (Fig. 1), an interaction between Dp and nSP30 may have contributed to the subsequent IgE-biased immune response.Fig. 5


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)

Effects of Dp + nSP30 aggregates compared with Dp and nSP30 administered on alternate days. a Effect of topical application of Dp + nSP30 and PBS (Dp + nSP30/PBS) compared with Dp and nSP30 (Dp/nSP30) on alternate days on ear thickness in NC/Nga mice. b–e Plasma levels of (b) total IgE, (c) Dp-specific IgE, (d) IgG and (e) IgG1 and IgG2a 24 h after final treatment, as analyzed by ELISA. f Numbers of Dp-specific IFN-γ- and IL-4-producing splenocytes after re-stimulation with 100 μg mL−1 Dp, as determined by ELISPOT assays specific for each cytokine. Data are presented as means ± SEMs (n = 5). *P < 0.05, **P < 0.01 vs. Dp/PBS group
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Fig5: Effects of Dp + nSP30 aggregates compared with Dp and nSP30 administered on alternate days. a Effect of topical application of Dp + nSP30 and PBS (Dp + nSP30/PBS) compared with Dp and nSP30 (Dp/nSP30) on alternate days on ear thickness in NC/Nga mice. b–e Plasma levels of (b) total IgE, (c) Dp-specific IgE, (d) IgG and (e) IgG1 and IgG2a 24 h after final treatment, as analyzed by ELISA. f Numbers of Dp-specific IFN-γ- and IL-4-producing splenocytes after re-stimulation with 100 μg mL−1 Dp, as determined by ELISPOT assays specific for each cytokine. Data are presented as means ± SEMs (n = 5). *P < 0.05, **P < 0.01 vs. Dp/PBS group
Mentions: We also evaluated the effects of sequential (rather than concurrent) cutaneous exposure to Dp and nSP30; that is, we topically applied Dp and nSP30 on alternate days rather than applying them together on the same day. Ear thickening and changes in total IgE concentration resulting from alternate-day application of Dp and nSP30 (Dp/nSP30) did not differ significantly from those resulting from concurrent treatment with Dp and PBS every other day (Dp/PBS) (Fig. 5a and b). Taken together, our results indicate that cutaneous exposure to nSP30 did not aggravate Dp-induced AD-like skin lesions regardless of whether the nanoparticles were applied together with or separately from Dp. In addition, alternate-day skin painting with Dp and nSP30 induced Dp-specific IgE and IgG production and Dp-specific IFN-γ- and IL-4-secreting splenocytes in the same way as did topical application of Dp and PBS (Fig. 5c–f). Therefore, exposure to both Dp and nSP30 was necessary to induce an IgE-biased immune response. Given that Dp + nSP30 formed agglomerates (Fig. 1), an interaction between Dp and nSP30 may have contributed to the subsequent IgE-biased immune response.Fig. 5

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