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

Details

• Personal Author:
  Kashon, Michael ; Lim, Chol S. ; Ma, Qiang ; Porter, Dale W. ; Veltri, Brandon
• 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, Mitsui-7) induce M1 polarization in vitro. Treatment of murine macrophages (J774A.1) with Mitsui-7 MWCNTs increased the expression of Alox5 mRNA and protein in a concentration- and time-dependent manner. The MWCNTs induced the expression of CD68 and that induction persisted for up to 3 days post-exposure. The expression and activity of inducible nitric oxide synthase, an intracellular marker of M1, were increased by MWCNTs. Consistent with M1 polarization, the MWCNTs induced the production and secretion of proinflammatory cytokines tumor necrosis factor-a and interleukin-1β, and proinflammatory LMs leukotriene B4 (LTB4) and prostaglandin E2 (PGE2). The cell-free media from MWCNT-polarized macrophages induced the migration of neutrophilic cells (differentiated from HL-60), which was blocked by Acebilustat, a specific leukotriene A4 hydrolase inhibitor, or LY239111, an LTB4 receptor antagonist, but not NS-398, a cyclooxygenase 2 inhibitor, 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. Taken together, these findings demonstrate the polarization of M1 macrophages by Mitsui-7 MWCNTs in vitro and that induction of Alox5 is an important mechanism by which the MWCNTs promote proinflammatory responses by boosting M1 polarization and production of proinflammatory LMs. [Description provided by NIOSH]
• Subjects:
  Blood Immune System Lung Macrophages Occupational Health Respiratory System Safety
• Keywords:
  Alox5 Author Keywords: Pulmonary Inflammation Immune Reaction In Vitro Study LTB4 Macrophage Polarization Multi-walled Carbon Nanotubes MWCNT Nanoparticles Pulmonary Effects
• ISSN:
  1743-5390
• Document Type:
  Text
• Genre:
  Journal Article
• 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
• Pages in Document:
  22 pdf pages
• Volume:
  17
• Issue:
  3
• NIOSHTIC Number:
  nn:20067454
• Citation:
  Nanotoxicology 2023 Mar; 17(3):249-269
• Contact Point Address:
  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, Morgantown, WV, USA
• Email:
  qam1@cdc.gov
• CAS Registry Number:
  Carbon nanotubes (CAS RN 308068-56-6)
• Federal Fiscal Year:
  2023
• NORA Priority Area:
  Construction
• Peer Reviewed:
  True
• Source Full Name:
  Nanotoxicology
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:5da7a49bb577fb4ef3525561730104f9bb1fc225d977d6621404de110262a67eef49f26a5d1af9edbac7a7a2b11fd41678281b83a8b1e8796a3fd9436afdda44
• Download URL:
  https://stacks.cdc.gov/view/cdc/230783/cdc_230783_DS1.pdf
• File Type:
  [PDF - 4.12 MB ]