Activation of the NLRP3 inflammasome correlates with the pulmonary bioactivity of multiwalled carbon nanotubes

Details

• Personal Author:
  Castranova, Vincent ; Hamilton R ; Holian A ; Porter, Dale ; Sager TM ; Wolfarth M ; Wu N
• Description:
  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. [Description provided by NIOSH]
• Subjects:
  Biochemistry Chemistry Environmental Monitoring Hazardous Substances Immune System Laboratories Lung Occupational Health Respiratory System Safety
• Keywords:
  Bioactivation Biochemical-analysis Biological-effects Cellular-reactions Chemical-composition Chemical-deposition Chemical-properties Chemical-reactions Chemical-structure Exposure-assessment Health-hazards Immune-reaction Immunochemistry Immunotoxins In-vivo-study Laboratory-animals Laboratory-testing Lung-cells Lung-fibrosis Lung-function Nanotechnology Pulmonary-system Sampling Surface-properties Toxic-effects Toxic-materials

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• ISSN:
  1096-6080
• Document Type:
  Text
• Genre:
  Abstract or Summary
• Place as Subject:
  California ; Montana ; OSHA Region 3 ; OSHA Region 8 ; OSHA Region 9 ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  HELD - Health Effects Laboratory Division
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  126
• NIOSHTIC Number:
  nn:20040600
• Citation:
  Toxicologist 2012 Mar; 126(Suppl 1):145
• CAS Registry Number:
  Carbon (CAS RN 7440-44-0)
• Federal Fiscal Year:
  2012
• NORA Priority Area:
  Manufacturing
• Peer Reviewed:
  False
• Source Full Name:
  The Toxicologist. Society of Toxicology 51st Annual Meeting and ToxExpo, March 11-15, 2012, San Francisco, California
• Supplement:
  1
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:3bd5edbc98fb5f63696fcd68601e29323c9f1e40688a5d0f0ab5b818266b29633ba534994f25f60644d74f2bd47283d41b2fb478dc62ab6ebfb3f99c975e5b78
• Download URL:
  https://stacks.cdc.gov/view/cdc/193399/cdc_193399_DS1.pdf
• File Type:
  [PDF - 467.22 KB ]