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Metal nanoparticles in the presence of lipopolysaccharides trigger the onset of metal allergy in mice

Abstract

Many people suffer from metal allergy, and the recently demonstrated presence of naturally occurring metal nanoparticles in our environment could present a new candidate for inducing metal allergy. Here, we show that mice pretreated with silver nanoparticles (nAg) and lipopolysaccharides, but not with the silver ions that are thought to cause allergies, developed allergic inflammation in response to the silver. nAg-induced acquired immune responses depended on CD4+ T cells and elicited IL-17A-mediated inflammation, similar to that observed in human metal allergy. Nickel nanoparticles also caused sensitization in the mice, whereas gold and silica nanoparticles, which are minimally ionizable, did not. Quantitative analysis of the silver distribution suggested that small nAg (≤10 nm) transferred to the draining lymph node and released ions more readily than large nAg (>10 nm). These results suggest that metal nanoparticles served as ion carriers to enable metal sensitization. Our data demonstrate a potentially new trigger for metal allergy.

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Figure 1: Sensitization potential of silver nanoparticles.
Figure 2: Relationship between acquired immunity and the effects of nAg10 pretreatment.
Figure 3: Effector response induced by nAg10 sensitization.
Figure 4: Distribution of nAg in draining lymph node.
Figure 5: Effect of nickel nanoparticles on nickel sensitization.

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Acknowledgements

The authors thank Y. Morishita for supporting the evaluations of the physicochemical properties of nanoparticles. This study was supported by Grants-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan (MEXT) and from the Japan Society for the Promotion of Science (JSPS), by a Grant-in-Aid for JSPS Fellows, by Health Labour Sciences Research Grants from the Ministry of Health, Labour and Welfare of Japan (MHLW), by The Takeda Science Foundation, by The Research Foundation for Pharmaceutical Sciences, by The Japan Food Chemical Research Foundation, by the Urakami Foundation and by the Uehara Memorial Foundation.

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Contributions

T.Hi. and Y.Y. conceived and designed the experiments. T.Hi., N.I. and K.I. performed most of the experiments. T.Ha., N.N., E.U., K.S., H.T. and M.Y. helped with collecting tissue samples and splenocytes. T.Hi., Y.Y., N.I. and K.I. analysed the data. T.Hi. and Y.Y. wrote the manuscript. K.N., Y.M., H.K., S.T., K.J.I. and K.H. provided technical support and conceptual advice. Y.T. supervised all the projects. All authors discussed the results and commented on the manuscript.

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Correspondence to Yasuo Yoshioka or Yasuo Tsutsumi.

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Yasuo Yoshioka is employed by The Research Foundation for Microbial Diseases of Osaka University. All other authors declare no competing financial interests.

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Hirai, T., Yoshioka, Y., Izumi, N. et al. Metal nanoparticles in the presence of lipopolysaccharides trigger the onset of metal allergy in mice. Nature Nanotech 11, 808–816 (2016). https://doi.org/10.1038/nnano.2016.88

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