Multiwalled Carbon Nanotubes Activate the NLRP3 Inflammasome-Dependent Pyroptosis in Macrophages

Details

• Personal Author:
  Gu JK ; Lim CS ; Ma Q
• Description:
  Macrophages are major innate immune cells for the clearance of inhaled nanoparticles but may undergo cell death upon phagocytosis of certain nanoparticles due to their resistance to lysosomal degradation and high toxicity to the cell. Here we investigated the pyroptotic effect of exposure to fibrogenic multiwalled carbon nanotubes (MWCNTs) on macrophages, an inflammatory form of cell death. We first evaluated MWCNT-induced cell death in M1 and M2 macrophages that mediate the temporal inflammatory response to MWCNTs in mammalian lungs. Macrophages were differentiated from human monocytic THP-1 cells, followed by polarization to M1 or M2 cells. MWCNTs caused concentration- and time-dependent cytotoxicity in M1 and, to a lesser extent, M2 cells. Carbon black, an amorphous carbonous material control for CNTs, did not cause apparent toxicity in the cells. MWCNTs increased the production and secretion of IL-1β, accompanied by activation of caspase-1, in M1, but not M2, cells. Moreover, MWCNTs induced the formation of apoptosis-associated speck-like protein containing a C-terminal caspase recruitment domain specks and the release of cathepsin B in M1 cells, revealing activation of the nucleotide-binding, oligomerization domain-like receptor family pyrin domain containing 3 (NLRP3) inflammasome via lysosomal damage. MWCNTs induced the cleavage of gasdermin D (GSDMD) to form the 31 kDa N-terminal fragment (GSDMD-N), the pore-forming peptide causing pyroptotic cell death. Increased IL-1β release was completely suppressed by AC-YVAD-CMK (a caspase-1 inhibitor), MCC-950 (an NLRP3 inflammasome inhibitor), or CA-074 Me (a cathepsin B inhibitor), alongside the blockage of MWCNT-induced cleavage of GSDMD. The study demonstrates that MWCNTs trigger pyroptosis in M1 macrophages and boost sterile inflammation by activating the NLRP3 inflammasome pathway. [Description provided by NIOSH]
• Subjects:
  Blood Immune System Macrophages Occupational Health Respiratory System Safety
• Keywords:
  Author Keywords: IL-1b Cellular Effects Immune Reaction Inflammation Inhalation M1 Macrophage Multi-walled Carbon Nanotubes MWCNT Nanoparticles NLRP3 Phagocytic Activity Pyroptosis

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• ISSN:
  0026-895X
• Document Type:
  Text
• Genre:
  Journal Article
• Place as Subject:
  Philadelphia Region [OSHA] ; 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:
  107
• Issue:
  5
• NIOSHTIC Number:
  nn:20070895
• Citation:
  Mol Pharmacol 2025 May; 107(5):100031
• Contact Point Address:
  Dr Qiang Ma, Receptor Biology Laboratory, Toxicology and Molecular Biology Branch, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Centers for Disease Control and Prevention, 1000 Frederick Lane, Morgantown, WV
• Email:
  qam1@cdc.gov
• CAS Registry Number:
  Carbon nanotubes (CAS RN 308068-56-6)
• Federal Fiscal Year:
  2025
• Peer Reviewed:
  True
• Source Full Name:
  Molecular Pharmacology
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:4bff20ce2e99a054fbf847edd0caca0b8b5b5b8cdb6550ec1d1f463d24f965194cf8700672b2ded08f63d95fe26023a78e1639fe28e9a6a8f23c23d2b2a20831
• Download URL:
  https://stacks.cdc.gov/view/cdc/209019/cdc_209019_DS1.pdf
• File Type:
  [PDF - 1.80 MB ]