Original Article
Potential impact of metal oxide nanoparticles on the immune system: The role of integrins, L-selectin and the chemokine receptor CXCR4

https://doi.org/10.1016/j.nano.2014.03.007Get rights and content

Abstract

The impact of metal oxide nanoparticles (NPs) on the immune system has been studied in vitro using human peripheral blood lymphocytes (PBLs). Metal oxide NPs (ZnO, CeO2, TiO2 and Al2O3) induced changes in the expression levels of adhesion molecules and the C-X-C chemokine receptor type 4 (CXCR4) in these cells. Proliferation studies were carried out with CFSE in response to PHA, finding an increase in T-cell proliferation upon cell exposure to TiO2 and Al2O3 NPs. For ZnO NPs, a decrease in the chemotactic response to SDF-1α was observed. No changes were found in basophil activation and leukocyte oxidative burst after phagocytosis. Despite the absence of cytotoxicity, metal oxide NPs are not inert; they alter the expression levels of adhesion molecules and chemokine receptors, key actors in the immune response, and affect important cell functions such as T-cell proliferative response to mitogens and chemotaxis.

From the Clinical Editor

This study demonstrates the immune-modulating effects of four different metal nanoparticles in a human peripheral blood lymphocyte model system. These effects were clearly present even though these nanoparticles did not display cytotocity in ex vivo experiments.

Graphical Abstract

Nanoparticles are extensively used, but their interaction with the immune system is poorly understood, regardless of potential adverse effects. We assessed the impact of metallic Nps (ZnO, CeO2, TiO2 and Al2O3) measuring the expression of adhesion molecules and the chemokine receptor CXCR4 in peripheral blood lymphocytes, T-cell proliferative responses, chemotaxis, basophil activation state and leukocyte oxidative burst after phagocytosis. We found that, although not toxic, metallic NPs do not seem inert, being able to alter key cell functions such as T-cell proliferative responses and chemotaxis, which could translate into important side effects in a medical context.

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Section snippets

Methods

We state that this study was approved by an ethics committee.

Metal oxide NPs induce changes in the expression levels of adhesion molecules and in the chemokine receptor CXCR4 on human PBLs

We assessed the effects of different concentrations of the metallic ZnO, CeO2, TiO2 and Al2O3 NPs, ranging from 0.5 to 50 μg/ml, on the expression levels of several adhesion molecules and of CXCR4 by flow cytometry. For the ZnO NPs, the experiments were performed using suboptimal, non-toxic concentrations3 of this nanomaterial.

A decrease was observed in the levels of the integrins LFA-1, β-1 and L-selectin upon cell incubation with all NPs tested (Figure 1, A-C). In contrast, regarding CXCR4

Discussion

Nanoparticles (NPs) are artificially engineered structures on the nanometer-length scale, increasingly used for medical applications. Therefore, understanding the interactions between NPs and the components of the immune system is crucial, given that the bioavailability and clearance of the particles may be affected, as well as the proper triggering of the immune responses. NPs can be immunostimulatory or immunosuppressive, but the role of engineered nanomaterials in the immune modulation is

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  • Cited by (0)

    Funding: This work was supported by ETORTEK 2010 (ETORIE 10-276) and HINAMOX (FP7/NMP4-SL-2009-228825). We also wish to thank the EU program BIOCAPS (FP7/REGPOT-2012-2013-316265) for its support. T.L. acknowledges an FPU fellowship (Spanish Ministry of Education). The authors declare no conflict of interest.

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