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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

Prevention of Dp + nSP30-mediated IgE-biased immune response by surface modification of nSP30. a–c Plasma levels of Dp-specific (a) IgE, (b) IgG, and (c) IgG1 and IgG2a at 24 h after final treatment of NC/Nga mice with Dp alone, Dp + nSP30, or Dp + nSP30C, as analyzed by ELISA. Data are given as means ± SEMs (n = 5). *P < 0.05, **P < 0.01 vs. Dp-alone group
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Fig6: Prevention of Dp + nSP30-mediated IgE-biased immune response by surface modification of nSP30. a–c Plasma levels of Dp-specific (a) IgE, (b) IgG, and (c) IgG1 and IgG2a at 24 h after final treatment of NC/Nga mice with Dp alone, Dp + nSP30, or Dp + nSP30C, as analyzed by ELISA. Data are given as means ± SEMs (n = 5). *P < 0.05, **P < 0.01 vs. Dp-alone group

Mentions: Because the surface properties of nanomaterials strongly influence their interactions with proteins [37], we investigated how surface modification of nSP30 with carboxyl groups affected the interaction between Dp and nSP30 and the subsequent IgE-biased immune response. Solutions of the mixture of Dp and nSP30 modified with surface carboxyl groups (nSP30C) were clear and colorless (Fig. 1a), and a TEM image of Dp + nSP30C was similar to that of nSP30C alone (Fig. 1b). The mean hydrodynamic diameter of Dp + nSP30C was 24.8 nm, which was only approximately 4 nm larger than that of nSP30C alone (Fig. 1c and d). These results suggest that the mixing of Dp and nSP30C did not result in substantial agglomeration. The level of Dp-specific IgE induced by cutaneous exposure to Dp + nSP30C was the same as that induced by cutaneous exposure to Dp alone or to Dp + nSP30 (Fig. 6a). Although cutaneous exposure to Dp + nSP30 significantly reduced the levels of Dp-specific IgG and its subtypes, cutaneous exposure to Dp + nSP30C had little effect on the levels of Dp-induced IgG, IgG1, and IgG2a (Fig. 6b and c).Fig. 6


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)

Prevention of Dp + nSP30-mediated IgE-biased immune response by surface modification of nSP30. a–c Plasma levels of Dp-specific (a) IgE, (b) IgG, and (c) IgG1 and IgG2a at 24 h after final treatment of NC/Nga mice with Dp alone, Dp + nSP30, or Dp + nSP30C, as analyzed by ELISA. Data are given as means ± SEMs (n = 5). *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

Fig6: Prevention of Dp + nSP30-mediated IgE-biased immune response by surface modification of nSP30. a–c Plasma levels of Dp-specific (a) IgE, (b) IgG, and (c) IgG1 and IgG2a at 24 h after final treatment of NC/Nga mice with Dp alone, Dp + nSP30, or Dp + nSP30C, as analyzed by ELISA. Data are given as means ± SEMs (n = 5). *P < 0.05, **P < 0.01 vs. Dp-alone group
Mentions: Because the surface properties of nanomaterials strongly influence their interactions with proteins [37], we investigated how surface modification of nSP30 with carboxyl groups affected the interaction between Dp and nSP30 and the subsequent IgE-biased immune response. Solutions of the mixture of Dp and nSP30 modified with surface carboxyl groups (nSP30C) were clear and colorless (Fig. 1a), and a TEM image of Dp + nSP30C was similar to that of nSP30C alone (Fig. 1b). The mean hydrodynamic diameter of Dp + nSP30C was 24.8 nm, which was only approximately 4 nm larger than that of nSP30C alone (Fig. 1c and d). These results suggest that the mixing of Dp and nSP30C did not result in substantial agglomeration. The level of Dp-specific IgE induced by cutaneous exposure to Dp + nSP30C was the same as that induced by cutaneous exposure to Dp alone or to Dp + nSP30 (Fig. 6a). Although cutaneous exposure to Dp + nSP30 significantly reduced the levels of Dp-specific IgG and its subtypes, cutaneous exposure to Dp + nSP30C had little effect on the levels of Dp-induced IgG, IgG1, and IgG2a (Fig. 6b and c).Fig. 6

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