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Activation of the NLRP3 inflammasome correlates with the pulmonary bioactivity of multiwalled carbon nanotubes.
Sager TM; Wolfarth M; Porter D; Wu N; Hamilton R; Holian A; Castranova V
Toxicologist 2012 Mar; 126(Suppl 1):145
Nanotechnology is one of the world's most promising new technologies. In turn, carbon nanotube production is estimated to reach into the millions of tons within the decade. In addition, surface modification of carbon nanotubes alters their charge, functionality, and reactivity; therefore extending their already broad applications. Utilizing two MWCNT samples, two hypotheses were tested in this study. First, we investigated whether MWCNTs with different surface chemistries exhibit different bioactivities in vivo. Second, we investigated if differences in bioactivity were related to activation of the NLRP3 inflammasome. To test these hypotheses, mice (C57BL/6J) were given 0-40 microg/mouse either bare (BMWCNT) or COOHcoated (FMWCNT) multi-walled carbon nanotubes via pharyngeal aspiration. The results show the BMWCNT were more bioactive in the lung, causing a more robust inflammatory and fibrotic response than FMWCNT. The BMWCT also caused significantly higher levels of the cellular mediators associated with NLRP3 inflammasome activation. Specifically, cathepsin-B activity, IL-1beta, IL-18, and IL-33 levels were significantly higher in BMWCNT than FMWCNT treated mice. In conclusion, this study provides evidence that the NLRP3 inflammasome is activated in vivo, after pulmonary exposure to MWCNTs, and the severity of the activation differs from BMWCNT to FMWCNT. The results confirm that modification of the surface of the MWCNT with COOH-groups decreased the bioactivity of the MWCNT. This difference in bioactivity correlated with the activation of the NLRP3 inflammasome. Taken together, the results demonstrate that coating the MWCNT surface, without affecting their intrinsic structure, may constitute a useful strategy for decreasing MWCNT toxicity.
Nanotechnology; Toxic-materials; Health-hazards; In-vivo-study; Sampling; Chemical-composition; Chemical-deposition; Chemical-properties; Chemical-reactions; Chemical-structure; Bioactivation; Biochemical-analysis; Biological-effects; Surface-properties; Laboratory-animals; Laboratory-testing; Exposure-assessment; Immune-reaction; Immunochemistry; Immunotoxins; Lung-cells; Lung-function; Pulmonary-system; Lung-fibrosis; Cellular-reactions; Toxic-effects
The Toxicologist. Society of Toxicology 51st Annual Meeting and ToxExpo, March 11-15, 2012, San Francisco, California
MT; WV; CA
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