The effect of nanoparticles on airway allergy in mice

To the Editors:

We read with great interest a recent experimental (in vivo) study by Hussain et al. 1 and would like to comment on that article. First of all, we were very interested in the overall results that a single airway exposure to relatively low dose (16 μg·mouse⁻¹) of nanoparticles facilitates allergic airway inflammation. We have previously examined several types of nanoparticles/nanomaterials on ovalbumin-induced airway inflammation 2–5. However, the doses were higher (25–100 μg·mouse⁻¹ administered weekly a total of seven times) and provoked a more moderate increase in the number of inflammatory leukocytes into bronchoalveolar spaces in the absence of allergen than that in the present study by Hussain et al. 1. Thus, their study is valuable in terms of promoting the effect of relatively realistic dose of nanoparticles on allergic inflammation, although sensitivity against nanoparticles seems to depend on mouse strains (we used ICR mice). We have recently shown that single intratracheal instillation of carbon black nanoparticles (CBNPs) (14 nm) at a dose of 10 μg·mouse⁻¹ aggravates bleomycin-induced pulmonary fibrosis (unpublished data); thus, taking these studies into consideration, it is confirmed at the animal model (in vivo) level that exposure to trace doses of some nanoparticles exacerbates several types of pulmonary inflammatory conditions.

Consistent with the study by Hussain et al. 1, we have found that effects of nanoparticles/nanomaterials on airway hyperresposiveness depend on the characteristics of these materials: two sizes (14 and 56 nm) of carbon nanoparticles significantly enhanced airway resistance 2; in contrast, two types (single- and multiwalled) of carbon nanotubes 3, 4 and two sizes (25 and 100 nm) of latex nanoparticles did not (5 and unpublished data). Indeed, some previous reports have implicated the independency of airway hyperresponsiveness from airway inflammation 6, 7; thus, the theory might be applied to the impacts of nanoparticles/nanomaterials on the allergic trait in the study by Hussain et al. 1.

Regarding factors contributing to inflammatory cell infiltration in the airway, impacts of immune modulators on the T-helper cell (Th) milieu should be important to assess allergic reactions. In particular, Th2 (e.g. interleukin (IL)-5) and Th17 (e.g. IL-17A) cytokines are reportedly crucial for eosinophil maturation, activation, survival and migration, and neutrophil invasion, respectively 8. Measurement of the levels in the lung (brochoalveolar lavage supernatants and/or lung homogenates) warrants further information about the effects of nanoparticles on allergic pathophysiology. Alternatively, the nanoparticles may preferentially affect other chemotactic factors for leukocytes, such as eotaxin, RANTES (regulated on activation, normal T-cell expressed and secreted), anaphylatoxins and lipid mediators, and/or their producing cells.

Finally, as Hussain et al. 1 described in their discussion, the effects of nanoparticles/nanomaterials on the phenotype and function of dendritic cells (DCs), as immune initiators, should be important for subsequent allergic pathology. Likewise, the degree of the effects appears to depend on the materials. We have also examined the effects of several environmental toxicants on bone marrow-derived DCs: CBNPs 9, 10, carbon nanotubes 3, 4, di-(2-ethylhexyl)-phthalate 11 and diisononyl-phthalate 12 activated DCs in vitro and in vivo, whereas latex nanoparticles did not (unpublished data). Interestingly, we have confirmed that the effects on DCs and antigen-presenting cells (APCs) parallel those on allergic pathology in vivo in their overall trend 12. Therefore, we propose that the enhancing effects of nanoparticles on the allergic asthma examined by Hussain et al. 1 are mediated via the inappropriate activation of APCs, including DCs.

• ©2011 ERS