Sterile Inflammation in Mouse Lung Driven by Lipid Mediator Pathways Following MWCNT Exposure

Details

• Personal Author:
  Ma, Qiang ; LeBouf, Ryan F. ; Rimayi, Chengetayi C. ; Lim, Chol S. ; Fekedulegn, Desta B. ; Park, Ju-Hyeong ; Porter, Dale W.
• Description:
  Exposure to respirable particles such as multiwalled carbon nanotubes (MWCNTs) can provoke acute lung inflammation and tissue injury, potentially progressing to chronic disease. Lipid mediators (LMs), including proinflammatory and pro-resolving species, play a critical role in regulating this process. This study investigated LM biosynthesis in acute lung inflammation induced by fibrogenic MWCNTs. Adult C57BL/6J mice were exposed to MWCNTs (Mitsui-7; 1860.4 µg/kg) via oropharyngeal aspiration. Lung tissues collected 24 h postexposure exhibited neutrophil infiltration, elevated inflammatory cytokines, and tissue damage. Enzymes involved in prostanoid synthesis-phospholipase A2, cyclooxygenase-2, and prostaglandin E synthase-were significantly upregulated. Lipidomic profiling was performed by using C18 spin column enrichment and UPLC-MS/MS. MWCNT exposure significantly increased the levels of prostanoids (PGE2, PGD2, PGF2a, thromboxane B2) and hydroxyeicosatetraenoic acids (5-, 12-, 15-HETE). Elevated levels of protectin DX, 14(S)-, and 17-HDHA derived from docosahexaenoic acid, and 12-, 15-, and 18-HEPE derived from eicosapentaenoic acid were also observed. In vitro, MWCNTs induced intracellular lipid accumulation in macrophages. These findings reveal rapid activation of LM biosynthetic pathways, particularly those producing proinflammatory prostanoids, in mouse lungs following nanoparticle exposure. The study underscored the utility of lipidomic profiling for mechanistic insights into nanoparticle-induced sterile inflammation and toxicity in limited tissue samples.
• Subjects:
  Lung Nanotubes, Carbon Occupational Health Safety
• Keywords:
  Multi-walled carbon nanotubes; MWCNT; Immune reaction; Lipids; Lung tissue; Nanotoxicology; Inhalation studies; Nanoparticles
• Series:
  Mining Publications
• ISSN:
  0893-228X
• Document Type:
  Text
• Genre:
  Journal Article
• Place as Subject:
  West Virginia ; Philadelphia Region [OSHA]
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  HELD - Health Effects Laboratory Division
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  15 pdf pages
• Volume:
  39
• Issue:
  1
• NIOSHTIC Number:
  nn:20071113
• Citation:
  Chem Res Toxicol 2026 Jan; 39(1):189-203
• Email:
  qam1@cdc.gov
• CAS Registry Number:
  Carbon nanotubes (CAS RN 308068-56-6)
• Federal Fiscal Year:
  2026
• Peer Reviewed:
  True
• Source Full Name:
  Chemical Research in Toxicology
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:904b2fe1b6efbbf69fb69b78adc2a8fd10740895cd3ab7aaf26066520889f52332fee9a8f1062dce39ab45f7f6fddfe53bfc4716a943997c4a7f293ce259c27b
• Download URL:
  https://stacks.cdc.gov/view/cdc/257889/cdc_257889_DS1.pdf
• File Type:
  [PDF - 11.41 MB ]