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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

Evaluation of absorption of Dp to nSP30. The amount of Dp in the supernatant of each centrifuged sample was determined (OD280). Data are given as means ± SD (n = 3). **P < 0.01 vs. Dp-alone
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Fig8: Evaluation of absorption of Dp to nSP30. The amount of Dp in the supernatant of each centrifuged sample was determined (OD280). Data are given as means ± SD (n = 3). **P < 0.01 vs. Dp-alone

Mentions: Atopic patients typically have relatively low IgG/IgE ratios [40, 41]. In addition, human studies indicate that IgE production in the absence of IgG production is a key risk factor for the onset of atopic allergy [42]. Low-dose exposure to allergen sometimes induces a low IgG/IgE ratio in both mice and humans [43, 44]. Therefore, the formation of agglomerates in our experimental system may, in effect, decrease allergen doses and then induce an IgE-biased immune response. To assess the amount of unbound Dp, we compared the Dp concentration in the supernatant after centrifugation. After centrifugation, the Dp concentration in the supernatant of the Dp-alone group was somewhat lower than that observed before centrifugation (1000 μg/mL → 457 μg/mL) (Fig. 8). Mixing Dp and nSP30 together in PBS decreased the Dp concentrations in the supernatants in an nSP30-dependent manner (Fig. 8). In contrast, mixing Dp with nSP30C in PBS or with nSP30 in water had little effect on the Dp concentration in the supernatant compared with that of the Dp-alone group. Therefore, agglomeration might increase the amount of Dp absorbed to nSP30. Considering the fact that, in general, aggregates and agglomerates of nanomaterials have difficulty penetrating the skin barrier [45], the agglomeration of Dp and nSP30 might decrease the exposure dose of Dp somewhat even when the agglomerates release Dp on the skin.Fig. 8


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)

Evaluation of absorption of Dp to nSP30. The amount of Dp in the supernatant of each centrifuged sample was determined (OD280). Data are given as means ± SD (n = 3). **P < 0.01 vs. Dp-alone
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Fig8: Evaluation of absorption of Dp to nSP30. The amount of Dp in the supernatant of each centrifuged sample was determined (OD280). Data are given as means ± SD (n = 3). **P < 0.01 vs. Dp-alone
Mentions: Atopic patients typically have relatively low IgG/IgE ratios [40, 41]. In addition, human studies indicate that IgE production in the absence of IgG production is a key risk factor for the onset of atopic allergy [42]. Low-dose exposure to allergen sometimes induces a low IgG/IgE ratio in both mice and humans [43, 44]. Therefore, the formation of agglomerates in our experimental system may, in effect, decrease allergen doses and then induce an IgE-biased immune response. To assess the amount of unbound Dp, we compared the Dp concentration in the supernatant after centrifugation. After centrifugation, the Dp concentration in the supernatant of the Dp-alone group was somewhat lower than that observed before centrifugation (1000 μg/mL → 457 μg/mL) (Fig. 8). Mixing Dp and nSP30 together in PBS decreased the Dp concentrations in the supernatants in an nSP30-dependent manner (Fig. 8). In contrast, mixing Dp with nSP30C in PBS or with nSP30 in water had little effect on the Dp concentration in the supernatant compared with that of the Dp-alone group. Therefore, agglomeration might increase the amount of Dp absorbed to nSP30. Considering the fact that, in general, aggregates and agglomerates of nanomaterials have difficulty penetrating the skin barrier [45], the agglomeration of Dp and nSP30 might decrease the exposure dose of Dp somewhat even when the agglomerates release Dp on the skin.Fig. 8

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