Macrophage Polarization Status Impacts Nanoceria Cellular Distribution but Not Its Biotransformation or Ferritin Effects

Details

• Personal Author:
  Dozier, Alan K. ; Feola DJ ; Graham UM ; Tseng MT ; Yokel RA
• Description:
  The innate immune system is the first line of defense against external threats through the initiation and regulation of inflammation. Macrophage differentiation into functional phenotypes influences the fate of nanomaterials taken up by these immune cells. High-resolution electron microscopy was used to investigate the uptake, distribution, and biotransformation of nanoceria in human and murine M1 and M2 macrophages in unprecedented detail. We found that M1 and M2 macrophages internalize nanoceria differently. M1-type macrophages predominantly sequester nanoceria near the plasma membrane, whereas nanoceria are more uniformly distributed throughout M2 macrophage cytoplasm. In contrast, both macrophage phenotypes show identical nanoceria biotransformation to cerium phosphate nanoneedles and simultaneous nanoceria with ferritin co-precipitation within the cells. Ferritin biomineralization is a direct response to nanoparticle uptake inside both macrophage phenotypes. We also found that the same ferritin biomineralization mechanism occurs after the uptake of Ce-ions into polarized macrophages and into unpolarized human monocytes and murine RAW 264.7 cells. These findings emphasize the need for evaluating ferritin biomineralization in studies that involve the internalization of nano objects, ranging from particles to viruses to biomolecules, to gain greater mechanistic insights into the overall immune responses to nano objects. [Description provided by NIOSH]
• Subjects:
  Blood Immune System Macrophages Occupational Health Safety Toxicology
• Keywords:
  Author Keywords: Analytical Microscopy Bioprocessing Biotransformation Cerium Oxides Cerium Phosphate Electron Microscopy Immune Reaction Iron Biomineralization Macrophage Phenotype Nanomaterials Nanotoxicology

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• ISSN:
  2079-4991
• Document Type:
  Text
• Genre:
  Journal Article
• Place as Subject:
  Kentucky ; Ohio ; OSHA Region 4 ; OSHA Region 5
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  HELD - Health Effects Laboratory Division
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  13
• Issue:
  16
• NIOSHTIC Number:
  nn:20068313
• Citation:
  Nanomaterials 2023 Aug; 13(16):2298
• Contact Point Address:
  Robert A. Yokel, Pharmaceutical Sciences Department, College of Pharmacy, University of Kentucky, Lexington, KY 40536-0596, USA
• Email:
  ryokel@uky.edu
• CAS Registry Number:
  Ceria (CAS RN 1306-38-3)
• Federal Fiscal Year:
  2023
• Peer Reviewed:
  True
• Source Full Name:
  Nanomaterials
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:ae181716de7f04898dd50b8919f43c90c4edb5e92dda89d5b15145f6df1a4d42daecd1aece9949ba164a666f25f349796a9b7e37b674fe09e790fddf5d3f9761
• Download URL:
  https://stacks.cdc.gov/view/cdc/230486/cdc_230486_DS1.pdf
• File Type:
  [PDF - 7.80 MB ]