Inhalation of rod-like carbon nanotubes causes unconventional allergic airway inflammation

Abstract

BackgroundCarbon nanotubes (CNT) represent a great promise for technological and industrial development but serious concerns on their health effects have also emerged. Rod-shaped CNT are, in fact, able to induce asbestos-like pathogenicity in mice including granuloma formation in abdominal cavity and sub-pleural fibrosis. Exposure to CNT, especially in the occupational context, happens mainly by inhalation. However, little is known about the possible effects of CNT on pulmonary allergic diseases, such as asthma.MethodsWe exposed mice by inhalation to two types of multi-walled CNT, rigid rod-like and flexible tangled CNT, for four hours a day once or on four consecutive days. Early events were monitored immediately and 24 hours after the single inhalation exposure and the four day exposure mimicked an occupational work week. Mast cell deficient mice were used to evaluate the role of mast cells in the occurring inflammation.ResultsHere we show that even a short-term inhalation of the rod-like CNT induces novel innate immunity-mediated allergic-like airway inflammation in healthy mice. Marked eosinophilia was accompanied by mucus hypersecretion, AHR and the expression of Th2-type cytokines. Exploration of the early events by transcriptomics analysis reveals that a single 4-h exposure to rod-shaped CNT, but not to tangled CNT, causes a radical up-regulation of genes involved in innate immunity and cytokine/chemokine pathways. Mast cells were found to partially regulate the inflammation caused by rod-like CNT, but also alveaolar macrophages play an important role in the early stages.ConclusionsThese observations emphasize the diverse abilities of CNT to impact the immune system, and they should be taken into account for hazard assessment.Electronic supplementary materialThe online version of this article (doi:10.1186/s12989-014-0048-2) contains supplementary material, which is available to authorized users.

In vivo activation of a T helper 2-driven innate immune response in lung fibrosis induced by multi-walled carbon nanotubes

“…MWCNT have been shown to stimulate allergy-like inflammation in mouse lung airways where expression of cytokines associated with Th2 functions, i.e., IL-4 and IL-13, was elevated (Rydman et al 2014). Allergen sensitization was found to induce the expression of IL-4 and IL-13, which appeared to suppress CNT-induced activation of inflammasomes (Shipkowski et al 2015).…”

STAT1-dependent and -independent pulmonary allergic and fibrogenic responses in mice after exposure to tangled versus rod-like multi-walled carbon nanotubes

“…For instance, lung exposure to rod-like (r) MWCNTs can lead to allergic airway inflammation and mucous cell metaplasia, while exposure to tangled (t) MWCNTs causes non-allergic lung inflammation with no mucous cell metaplasia [9–11]. Other properties of MWCNTs have been shown to play a role in their pulmonary toxicity (i.e.…”

“…Other properties of MWCNTs have been shown to play a role in their pulmonary toxicity (i.e. length, surface charge, residual metals) yet only a few studies comparing MWCNTs with contrasting rigidity have been conducted [9, 12]. However, to our knowledge there are no studies that address genetic susceptibility to allergic or fibrogenic responses to MWCNTs with different rigidities.…”

Multi-omics analysis of ten carbon nanomaterials effects highlights cell type specific patterns of molecular regulation and adaptation

“…Nanomaterials used in this study were previously characterized and reported in NANOATLAS (Vippola et al, 2009) as well as in our previous publications (Kinaret et al, 2017a;Rydman et al, 2015;Rydman et al, 2014;Palomäki et al, 2015). Providers and material characteristics are reported in Table 1.…”

“…We and others already showed that ENMs are able to exert toxic effects on the respiratory system, by using animal exposure models (Kinaret et al, 2017a;Rydman et al, 2015;Rydman et al, 2014). Apart from the pathological responses, ENMs MOA has been investigated in different tissues (Kinaret et al, 2017b;Fröhlich, 2017;Costa and Fadeel, 2016), by analyzing the molecular perturbations that these materials are able to induce on the normal transcriptional program of exposed cells and tissues.…”