Rapid Activation of Prostaglandin Synthesis Pathways in Mouse Lungs Exposed to Multi-Walled Carbon Nanotubes

Details

• Personal Author:
  Ma, Qiang ; LeBouf, Ryan F. ; Rimayi, Chengetayi C. ; Lim, C. C. ; Fekedulegn, Desta B.
• Description:
  Background and Purpose: Pulmonary exposure to respirable particles elicits acute inflammation with concurring tissue damage that may progress to chronic outcomes. The initiation and resolution of inflammation are critically regulated by potent proinflammatory and pro-resolving mediators in a time-dependent manner. Here we examined the synthesis of lipid mediators (LMs) in acute inflammation in mouse lungs exposed to fibrogenic multi-walled carbon nanotubes (MWCNTs). Methods: Adult C57BL/6J mice were exposed to MWCNTs (Mitsui-7) at 1860.4 µg/kg body weight by oropharyngeal aspiration. Lung tissue was collected at 24 hours post-exposure. Lipidomic profiling of LMs was performed to identify and quantitate major LMs by liquid chromatography-tandem mass spectrometry using Waters ACQUITY Xevo TQ-XS. Quantification of LMs was performed using both external and deuterium- labeled internal standards. Results: Exposure to MWCNTs induced acute inflammation and elevated phospholipase A2, cyclooxygenase 2, and prostaglandin (PG) E synthase at the protein and enzyme activity levels, indicating rapid activation of PG synthesis in mouse lungs. MWCNTs significantly elevated the levels of PGs including PGE2, PGD2, PGF2a, and thromboxane B2, as well as PG intermediate metabolites 5-, 12-, and 15-hydroxyeicosatetraenoic acids. Additionally, MWCNTs increased levels of protectin DX and 14(S)- and 17-hydroxydocosahexaenoic acids from the docosahexaenoic acid pathway, and 12-, 15-, and 18-hydroxyeicosapentaenoic acids from the eicosapentaenoic acid pathway. Conclusions: The results revealed rapid activation of synthesis pathways of LMs, particularly, PGs, in mouse lungs by nanoparticles. The study demonstrates the utility of lipidomics of LMs in the study of nanoparticle- induced sterile inflammation and pulmonary toxicity. Description provided by NIOSH
• Subjects:
  • Lung
  • Mice
  • Nanostructures
  • Nanotubes, Carbon
  • Occupational Health
  • Safety
• Keywords:
  • MWCNT; Multi-walled carbon nanotubes; Nanoparticles; Lipids; Laboratory animals; Lung tissue; Immune reaction
• Source:
  Toxicologist 2025 Mar; 204(S1):575
• ISSN:
  1096-6080
• Document Type:
  Text
• Genre:
  Abstract or Summary
• Place as Subject:
  Philadelphia Region OSHA ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  HELD - Health Effects Laboratory Division ; RHD - Respiratory Health Division
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  2 pdf pages
• Volume:
  204
• NIOSHTIC Number:
  nn:20071589
• CAS Registry Number:
  • Carbon nanotubes (CAS RN 308068-56-6)
• Federal Fiscal Year:
  2025
• NORA Priority Area:
  Construction ; Manufacturing
• Peer Reviewed:
  False
• Download URL:
  https://stacks.cdc.gov/view/cdc/259364/cdc_259364_DS1.pdf
• File Type:
  [PDF - 242.67 KB]
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:8a26b574efe54bbe282a20a88cd7f005267b932f41bb137cb0b7431b94745802381a70f770975637499fc11bda912cd206079109d52f39248a050f1b0c3a046c