Cutaneous exposure to agglomerates of silica nanoparticles and allergen results in IgE-biased immune response and increased sensitivity to anaphylaxis in mice

Abstract

BackgroundThe 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.ResultsRepeated 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.ConclusionsOur 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.Electronic supplementary materialThe online version of this article (doi:10.1186/s12989-015-0095-3) contains supplementary material, which is available to authorized users.

Allergic Responses Induced by the Immunomodulatory Effects of Nanomaterials upon Skin Exposure

“…However, these nanoparticles decreased local skin inflammatory responses, such as cytokine induction, in this mouse model ( 38 ). Our group showed that topical skin painting with a mixture of SiO 2 nanoparticles and mite allergen suppressed allergen-specific IgG production without any changes in the IgE and Th1/Th2 immune responses ( 72 ). In addition, the suppression of IgG caused severe IgE-mediated hypersensitivity in an anaphylaxis model.…”

Combined Action of Human Commensal Bacteria and Amorphous Silica Nanoparticles on the Viability and Immune Responses of Dendritic Cells

“…This choice of NP is based on the fact that the mean human adult intake of amorphous silica, which is used as a drug excipient or as a food additive and which is used for these purposes at concentrations ranging from 3 to 15 g/g of product (40), is estimated to be about 2 mg/kg of body weight/day (41). Although the nanosize nature of this material needs to be clarified (42), experiments suggest that SiO 2 NPs can enter intestinal epithelial cells and diffuse to the undermucosa or to the skin dermis (43)(44)(45)(46), where they may induce anaphylactic reactions (47,48). SiO 2 NPs are reported to induce cytotoxic, proinflammatory, and proimmune effects in murine DCs and skin Langerhans cells in vitro and in vivo (9,49,50).…”

Engineered Nanomaterials and Type I Allergic Hypersensitivity Reactions

“…Furthermore, the authors have found that such response was inversely correlated with particle size. It has also been shown in a subsequent study by the same group that cutaneous exposure to agglomerates of silica nanoparticles (30 nm in diameter) and mite allergen resulted in a low IgG/IgE ratio and increased sensitivity to anaphylaxis (32). Another report has demonstrated that repeated topical exposure to ZnO nanoparticles (but not their bulk counterparts) in a BALB/c mouse model of AD, although suppressed local inflammation, resulted in aggravated response to the allergen (ovalbumin/staphylococcal enterotoxin B), which was manifested by elevated serum IgE levels suggesting a possible nanoparticle-specific role in priming Th2-type allergic responses (30).…”