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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

Sensitivity to anaphylactic shock. Time-dependence of change in rectal temperature in NC/Nga mice due to intravenous challenge with Dp after treatment with Dp alone or Dp + nSP30 in PBS. Data are given as means ± SEMs (n = 6). *P < 0.05 vs. Dp-alone group
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Fig4: Sensitivity to anaphylactic shock. Time-dependence of change in rectal temperature in NC/Nga mice due to intravenous challenge with Dp after treatment with Dp alone or Dp + nSP30 in PBS. Data are given as means ± SEMs (n = 6). *P < 0.05 vs. Dp-alone group

Mentions: Chemical mediators such as histamine and various cytokines induce the typical symptoms of atopic allergy, including inflammation and itching [30, 31]. The production of these chemical mediators is induced when an allergen cross-links IgE molecules bound to high-affinity IgE receptors (FcεRI) on mast cells and basophils. However, allergen-specific IgG, considered to be the ‘blocking antibody’, may neutralize allergen molecules before they can interact with IgE [32, 33]. Furthermore, IgG–allergen complexes act through a pathway regulated by the inhibitory receptor FcγRIIB to inhibit IgE-mediated mast cell and basophil signaling [32–34]. Therefore, the presence of allergen-specific IgG inhibits IgE-mediated allergic responses. Because our results showed that Dp + nSP30 led to low levels of Dp-specific IgG with little change in the levels of Dp-specific IgE (Fig. 3a–c), we examined whether this IgE-biased immune response induced by cutaneous exposure to Dp + nSP30 caused IgE-mediated hypersensitivity to Dp in a systemic anaphylaxis model. The decrease in rectal temperature after challenge with intravenous Dp was significantly greater in mice sensitized by Dp + nSP30 than in those sensitized by Dp alone (Fig. 4). That is, mice in the Dp + nSP30 group were more sensitive to the induction of Dp-specific anaphylaxis than were those in the Dp-alone group. Together, concurrent cutaneous exposure to Dp and nSP30 induced IgE-biased immune responses and, subsequently, increased sensitivity to anaphylaxis. In contrast, the functions of specific immunoglobulin subtypes vary between mice and humans; for example, blocking antibodies in humans are considered to be of the IgG4 subtype, which mice lack [35]. Therefore, our results cannot be extrapolated directly to humans. In addition, regulatory T and B cells have recently been suggested to be the main suppressors of atopic allergy in allergen-specific immunotherapy [36]. Additional study is needed to clarify whether increases in anaphylactic sensitivity is solely due to blocking antibody.Fig. 4


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)

Sensitivity to anaphylactic shock. Time-dependence of change in rectal temperature in NC/Nga mice due to intravenous challenge with Dp after treatment with Dp alone or Dp + nSP30 in PBS. Data are given as means ± SEMs (n = 6). *P < 0.05 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

Fig4: Sensitivity to anaphylactic shock. Time-dependence of change in rectal temperature in NC/Nga mice due to intravenous challenge with Dp after treatment with Dp alone or Dp + nSP30 in PBS. Data are given as means ± SEMs (n = 6). *P < 0.05 vs. Dp-alone group
Mentions: Chemical mediators such as histamine and various cytokines induce the typical symptoms of atopic allergy, including inflammation and itching [30, 31]. The production of these chemical mediators is induced when an allergen cross-links IgE molecules bound to high-affinity IgE receptors (FcεRI) on mast cells and basophils. However, allergen-specific IgG, considered to be the ‘blocking antibody’, may neutralize allergen molecules before they can interact with IgE [32, 33]. Furthermore, IgG–allergen complexes act through a pathway regulated by the inhibitory receptor FcγRIIB to inhibit IgE-mediated mast cell and basophil signaling [32–34]. Therefore, the presence of allergen-specific IgG inhibits IgE-mediated allergic responses. Because our results showed that Dp + nSP30 led to low levels of Dp-specific IgG with little change in the levels of Dp-specific IgE (Fig. 3a–c), we examined whether this IgE-biased immune response induced by cutaneous exposure to Dp + nSP30 caused IgE-mediated hypersensitivity to Dp in a systemic anaphylaxis model. The decrease in rectal temperature after challenge with intravenous Dp was significantly greater in mice sensitized by Dp + nSP30 than in those sensitized by Dp alone (Fig. 4). That is, mice in the Dp + nSP30 group were more sensitive to the induction of Dp-specific anaphylaxis than were those in the Dp-alone group. Together, concurrent cutaneous exposure to Dp and nSP30 induced IgE-biased immune responses and, subsequently, increased sensitivity to anaphylaxis. In contrast, the functions of specific immunoglobulin subtypes vary between mice and humans; for example, blocking antibodies in humans are considered to be of the IgG4 subtype, which mice lack [35]. Therefore, our results cannot be extrapolated directly to humans. In addition, regulatory T and B cells have recently been suggested to be the main suppressors of atopic allergy in allergen-specific immunotherapy [36]. Additional study is needed to clarify whether increases in anaphylactic sensitivity is solely due to blocking antibody.Fig. 4

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