Long, Needle-like Carbon Nanotubes and Asbestos Activate the NLRP3 Inflammasome through a Similar Mechanism

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Abstract

Carbon nanomaterials (CNM) are targets of great interest because they have multiple applications in industry but also because of the fear of possible harmful heath effects of certain types of CNM. The high aspect ratio of carbon nanotubes (CNT), a feature they share with asbestos, is likely the key factor for reported toxicity of certain CNT. However, the mechanism to explain this toxicity is unclear. Here we investigated whether different CNM induce a pro-inflammatory response in human primary macrophages. Carbon black, short CNT, long, tangled CNT, long, needle-like CNT, and crocidolite asbestos were used to compare the effect of size and shape on the potency of the materials to induce secretion of interleukin (IL) 1-family cytokines. Our results demonstrated that long, needle-like CNT and asbestos activated secretion of IL-1β from LPS-primed macrophages but only long, needle-like CNT induced IL-1α secretion. SiRNA experiments demonstrated that the NLRP3 inflammasome was essential for long, needle-like CNT and asbestos-induced IL-1β secretion. Moreover, it was noted that CNT-induced NLRP3 inflammasome activation depended on reactive oxygen species (ROS) production, cathepsin B activity, P2X(7) receptor, and Src and Syk tyrosine kinases. These results provide new information about the mechanisms by which long, needle-like materials may cause their harmful health effects. Furthermore, the techniques used here may be of use in future risk assessments of nanomaterials.

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