Multi-walled carbon nanotubes induce airway hyperresponsiveness in human bronchi by stimulating sensory C-fibers and increasing the release of neuronal acetylcholine

Objectives: The potential of multi-walled carbon nanotubes (MWCNTs) in inducing airway hyperresponsiveness (AHR) was investigated in human airways. Methods: Human isolated bronchi were exposed to MWCNTs and the contractility to electrical field stimulation (EFS) was measured. Neuronal acetylcholine (ACh) and cyclic adenosine monophosphate (cAMP) were quantified. Some tissues were desensitized by consecutive administrations of capsaicin. Results: MWCNTs (100 ng/ml–100 µg/ml) induced AHR (overall contractile tone vs. negative control: +83.43 ± 11.13%, P < 0.01). The potency was significantly (P < 0.05) greater when airways were stimulated at low frequency (EFS3Hz) then at medium-to-high frequencies (EFS10Hz and EFS25Hz) (delta potency: +2.13 ± 0.74 and +2.40 ± 0.65 logarithms, respectively). In capsaicin-desensitized airways, the AHR to MWCNTs 100 ng/ml was abolished. MWCNTs increased the release of ACh, an effect prevented by capsaicin-desensitization (−90.17 ± 18.59%, P < 0.05). MWCNTs did not alter the level of cAMP. Conclusion: MWCNTs administered at low concentrations elicit AHR in human airways by activating sensory C-fibers and, in turn, increasing the release of neuronal ACh. Our results suggest that work is required to understand the impact of MWCNTs in patients at risk of AHR, such as those suffering from chronic obstructive respiratory disorders.