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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

Induction of AD-like skin lesions by Dp + nSP30 agglomerates in PBS. a Effect of topical administration of Dp alone or Dp + nSP30 in PBS on ear thickness in NC/Nga mice. b and c, Histology of ear sections stained with (b) hematoxylin and eosin (HE) or (c) toluidine blue (TB). Scale bar, 50 μm. (d) Scores for several symptoms characteristic of AD evaluated in HE-stained sections. e Mast cell infiltration evaluated in TB-stained sections as the number of mast cells per high-power (400×) field (HPF). f Total plasma IgE concentrations measured 24 h after the final skin painting. Data are presented as means ± SEMs (n = 5). *P < 0.05 vs. Dp-alone group
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Fig2: Induction of AD-like skin lesions by Dp + nSP30 agglomerates in PBS. a Effect of topical administration of Dp alone or Dp + nSP30 in PBS on ear thickness in NC/Nga mice. b and c, Histology of ear sections stained with (b) hematoxylin and eosin (HE) or (c) toluidine blue (TB). Scale bar, 50 μm. (d) Scores for several symptoms characteristic of AD evaluated in HE-stained sections. e Mast cell infiltration evaluated in TB-stained sections as the number of mast cells per high-power (400×) field (HPF). f Total plasma IgE concentrations measured 24 h after the final skin painting. Data are presented as means ± SEMs (n = 5). *P < 0.05 vs. Dp-alone group

Mentions: To examine the effects of co-exposure of skin to allergen and nSP30, we used an extract of the mite Dermatophagoides pteronyssinus (Dp) and NC/Nga mice as a model for human AD [17]. Dp is a frequent cause of many allergic conditions, including asthma and AD [18, 19]. In addition, NC/Nga mice have a genetic skin barrier defect related to low ceramide production [20]. To induce AD-like skin lesions, we repeatedly cutaneously exposed NC/Nga mice to either Dp alone or a mixture of Dp and nSP30 in an isotonic solution (phosphate buffered saline; PBS). Note that although the solutions of Dp alone and nSP30 alone were clear and colorless, the mixture of Dp + nSP30 was cloudy (Fig. 1a). TEM images suggested that mixing resulted in the formation of agglomerates (Fig. 1b), which was confirmed by the fact that the mean hydrodynamic diameter of the particles in the mixture was 1310.0 nm, which was larger than that of nSP30 alone (Fig. 1c and d). First, we confirmed that exposure to nSP30 alone did not induce the formation of topical skin lesions (Additional file 1). Comparison of the PBS and Dp-alone groups indicated that cutaneous exposure to Dp induced ear thickening, scab formation, acanthosis, inflammatory cell infiltration, and mast cell infiltration (Fig. 2a–e). The effects of cutaneous exposure to Dp + nSP30 did not differ from those of Dp alone, except that the extent of ear thickening was slightly less in the Dp + nSP30 group than in the Dp-alone group.Fig. 2


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)

Induction of AD-like skin lesions by Dp + nSP30 agglomerates in PBS. a Effect of topical administration of Dp alone or Dp + nSP30 in PBS on ear thickness in NC/Nga mice. b and c, Histology of ear sections stained with (b) hematoxylin and eosin (HE) or (c) toluidine blue (TB). Scale bar, 50 μm. (d) Scores for several symptoms characteristic of AD evaluated in HE-stained sections. e Mast cell infiltration evaluated in TB-stained sections as the number of mast cells per high-power (400×) field (HPF). f Total plasma IgE concentrations measured 24 h after the final skin painting. Data are presented as means ± SEMs (n = 5). *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

Fig2: Induction of AD-like skin lesions by Dp + nSP30 agglomerates in PBS. a Effect of topical administration of Dp alone or Dp + nSP30 in PBS on ear thickness in NC/Nga mice. b and c, Histology of ear sections stained with (b) hematoxylin and eosin (HE) or (c) toluidine blue (TB). Scale bar, 50 μm. (d) Scores for several symptoms characteristic of AD evaluated in HE-stained sections. e Mast cell infiltration evaluated in TB-stained sections as the number of mast cells per high-power (400×) field (HPF). f Total plasma IgE concentrations measured 24 h after the final skin painting. Data are presented as means ± SEMs (n = 5). *P < 0.05 vs. Dp-alone group
Mentions: To examine the effects of co-exposure of skin to allergen and nSP30, we used an extract of the mite Dermatophagoides pteronyssinus (Dp) and NC/Nga mice as a model for human AD [17]. Dp is a frequent cause of many allergic conditions, including asthma and AD [18, 19]. In addition, NC/Nga mice have a genetic skin barrier defect related to low ceramide production [20]. To induce AD-like skin lesions, we repeatedly cutaneously exposed NC/Nga mice to either Dp alone or a mixture of Dp and nSP30 in an isotonic solution (phosphate buffered saline; PBS). Note that although the solutions of Dp alone and nSP30 alone were clear and colorless, the mixture of Dp + nSP30 was cloudy (Fig. 1a). TEM images suggested that mixing resulted in the formation of agglomerates (Fig. 1b), which was confirmed by the fact that the mean hydrodynamic diameter of the particles in the mixture was 1310.0 nm, which was larger than that of nSP30 alone (Fig. 1c and d). First, we confirmed that exposure to nSP30 alone did not induce the formation of topical skin lesions (Additional file 1). Comparison of the PBS and Dp-alone groups indicated that cutaneous exposure to Dp induced ear thickening, scab formation, acanthosis, inflammatory cell infiltration, and mast cell infiltration (Fig. 2a–e). The effects of cutaneous exposure to Dp + nSP30 did not differ from those of Dp alone, except that the extent of ear thickening was slightly less in the Dp + nSP30 group than in the Dp-alone group.Fig. 2

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