Role of chemical composition and redox modification of poorly soluble nanomaterials on their ability to enhance allergic airway sensitisation in mice

Rob J Vandebriel,Isabella Römer,Selina V Y Tang,Jack R Harkema,Susan Dekkers,Mark R Miller,Flemming R Cassee,Wim H De Jong,James G Wagner,Elyse A Eldridge

doi:10.1186/s12989-019-0320-6

Abstract

BackgroundEngineered nanoparticles (NPs) have been shown to enhance allergic airways disease in mice. However, the influence of the different physicochemical properties of these particles on their adjuvant properties is largely unknown. Here we investigate the effects of chemical composition and redox activity of poorly soluble NPs on their adjuvant potency in a mouse model of airway hypersensitivity.ResultsNPs of roughly similar sizes with different chemical composition and redox activity, including CeO2, Zr-doped CeO2, Co3O4, Fe-doped Co3O4(using Fe2O3 or Fe3O4) and TiO2 NPs, all showed adjuvant activity. OVA induced immune responses following intranasal exposure of BALB/c mice to 0.02% OVA in combination with 200 μg NPs during sensitization (on day 1, 3, 6 and 8) and 0.5% OVA only during challenge (day 22, 23 and 24) were more pronounced compared to the same OVA treatment regime without NPs. Changes in OVA-specific IgE and IgG1 plasma levels, differential cell count and cytokines in bronchoalveolar lavage fluid (BALF), and histopathological detection of mucosa cell metaplasia and eosinophil density in the conducting airways were observed. Adjuvant activity of the CeO2 NPs was primarily mediated via the Th2 response, while that of the Co3O4 NPs was characterised by no or less marked increases in IgE plasma levels, BALF IL-4 and IL-5 concentrations and percentages of eosinophils in BALF and more pronounced increases in BALF IL-6 concentrations and percentages of lymphocytes in BALF. Co-exposure to Co3O4 NPs with OVA and subsequent OVA challenge also induced perivascular and peribronchiolar lymphoid cell accumulation and formation of ectopic lymphoid tissue in lungs. Responses to OVA combined with various NPs were not affected by the amount of doping or redox activity of the NPs.ConclusionsThe findings indicate that chemical composition of NPs influences both the relative potency of NPs to exacerbate allergic airway sensitization and the type of immune response. However, no relation between the acellular redox activity and the observed adjuvant activity of the different NPs was found. Further research is needed to pinpoint the precise physiological properties of NPs and biological mechanisms determining adjuvant activity in order to facilitate a safe-by-design approach to NP development.

Highlights

Engineered nanoparticles (NPs) have been shown to enhance allergic airways disease in mice
We present an airway exposure study in a mouse model for airway allergy using the following poorly soluble NPs differing in redox potential but with similar sizes: a) Co3O4 NPs doped with different amounts of Fe, b) CeO2 NPs doped with different amounts of Zr, c) CeO2 NM212 NPs and d) TiO2 NPs
All NPs investigated possessed adjuvant activity, leading to changes in OVA-specific IgE and IgG1 plasma levels, differential cell count and cytokines in bronchoalveolar lavage fluid (BALF), and histopathological detection of mucosa cell metaplasia and Adjuvant activity the increased OVA-specific IgE and IgG1 plasma levels of all OVA + NP exposed groups compared to OVA controls were not statistically significant for all NPs, they do indicate that NPs have the capacity to enhance allergic sensitisation in mice

Summary

Introduction

Engineered nanoparticles (NPs) have been shown to enhance allergic airways disease in mice. Nano-sized silica and titanium dioxide particles have been shown to enhance allergic airways sensitisation in mice [9, 10], there is limited understanding of the different physicochemical properties of NPs which influence their adjuvant properties. Previous studies on the influence of NPs on allergic airway sensitisation initially focussed on the role of the dendritic cell and T-cell interaction. Molecular interactions that drive these cellular responses have been suggested to involve increases in reactive oxygen species (ROS) caused by NPs with an oxidative surface chemistry, inflammasome activation, cellular injury and the induction of dendritic cell simulating cytokines or chemokines by epithelial cells (either direct or via oxidative stress) [7]

Methods

Results

Discussion

Conclusion