Multi-Walled Carbon Nanotubes Induce Arachidonate 5-Lipoxygenase Expression and Enhance the Polarization and Function of M1 Macrophages In Vitro (Dataset)

Details

• Personal Author:
  Kashon M ; Lim CS ; Ma Q ; Porter DW ; Veltri B
• Description:
  Fibrogenic carbon nanotubes (CNTs) induce the polarization of M1 and M2 macrophages in mouse lungs. Polarization of the macrophages regulates the production of proinflammatory and pro-resolving lipid mediators (LMs) to mediate acute inflammation and its resolution in a time-dependent manner. Here we examined the molecular mechanism by which multi-walled CNTs (MWCNTs) induce M1 polarization in vitro, with a focus on the induction of arachidonate 5-lipoxygenase (Alox5), a key enzyme in the biosynthesis of LMs. Treatment of J774A.1 murine macrophages with MWCNTs increased the expression of Alox5 mRNA in a concentration- and time-dependent manner, with the largest induction (5.3-fold over control) occurring at 10 mg/ml and 3 days post-exposure. The Alox5 protein was similarly induced. Alongside Alox5 induction, MWCNTs induced the expression of CD68, a cell surface marker of M1, by approximately 2.0-fold and that induction persisted for up to 3 days post-exposure. Both the expression and activity of inducible nitric oxide synthase, an intracellular marker of M1, were increased by MWCNTs up to 8.4-fold. Consistent with M1 polarization, MWCNTs induced the production and secretion of proinflammatory cytokines tumor necrosis factor-a and interleukin-1beta, and proinflammatory LMs leukotriene B4 (LTB4) and prostaglandin E2 (PGE2). Moreover, cell-free media from MWCNT-polarized macrophages induced the migration of neutrophils, which was blocked by Acebilustat, a specific leukotriene A4 hydrolase inhibitor, or LY239111, a LTB4 receptor antagonist, but not the cyclooxygenase 2 inhibitor, NS-398, revealing LTB4 as a major mediator of neutrophil chemotaxis from MWCNT-polarized macrophages. Knockdown of Alox5 using specific small hairpin-RNA suppressed MWCNT-induced M1 polarization, LTB4 secretion, and migration of neutrophils, implicating an important role of Alox5 in MWCNT-induced M1 polarization and function. Taken together, these findings demonstrate the polarization of M1 macrophages by MWCNTs in vitro and highlight induction of Alox5 as an important mechanism by which MWCNTs promote proinflammatory responses by boosting M1 polarization and production of pro-inflammatory LMs. [Description provided by NIOSH]
• Subjects:
  Blood Immune System Lung Macrophages Occupational Health Respiratory System Safety
• Keywords:
  Immune Reaction In Vitro Study Multi-walled Carbon Nanotubes MWCNT Nanoparticles Pulmonary Effects
• DOI:
  https://doi.org/10.26616/NIOSHRD-1067-2023-0
• Publisher:
  National Institute for Occupational Safety and Health
• Document Type:
  Dataset
• Genre:
  Research Dataset
• Place as Subject:
  OSHA Region 3 ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  HELD - Health Effects Laboratory Division
• Topic:
  Workplace Safety & Health
• Location:
  North America
• NIOSHTIC Number:
  nn:20067535
• Citation:
  Morgantown, WV: U.S. Department of Health and Human Services, Public Health Service, Centers for Disease Control and Prevention, National Institute for Occupational Safety and Health, Research Dataset RD-1067-2023-0, 2023 May; :dataset
• Contact Point Address:
  NIOSH/HELD Toxicology and Molecular Biology Branch. Tel: 304.285.6241
• CAS Registry Number:
  Carbon nanotubes (CAS RN 308068-56-6)
• Federal Fiscal Year:
  2023
• NORA Priority Area:
  Construction
• Peer Reviewed:
  False
• Source Full Name:
  Multi-walled carbon nanotubes induce arachidonate 5-lipoxygenase expression and enhance the polarization and function of M1 macrophages in vitro
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:698ecb21185769c68556ecb1043a10b9bc5f444903868924641044572142f9219bf3bb1086dbb45d35c1762ef2c902a689edb366c1d9482dbb5defbe3b4be382
• Download URL:
  https://stacks.cdc.gov/view/cdc/231485/cdc_231485_DS1.pdf
• File Type:
  [PDF - 130.43 KB ]