Macrophage-endothelial cell cross talk in ozone-oxidized carbon black nanoparticle exposure.

Details

• Personal Author:
  Bitounis D ; Demokritous P ; Erdely A ; Hussain S ; Kodali V ; Majumder N ; Mazumder M ; Nurkiewicz T ; Velayutham M
• Description:
  Apart from natural oxidation of particulate components of air pollution by the reactive gases like ozone (O3), oxidation of carbon black (CB) nanoparticle (NP) is also performed intentionally for industrial applications. Health impacts of these O3-oxidized CB (CBox) NPs are unknown. We hypothesized that macrophage uptake of CBox NPs and secretion of soluble factors mediate enhanced endothelial cell damage abilities of CBox. CBox NPs were generated under controlled conditions (2 ppm O3 for 3 hours) in a custom developed inhalation exposure chamber. A detailed physicochemical characterization and dosimetry modelling of CB and CBox NPs was performed. Surface oxidation changes were confirmed using X-ray photo electron spectroscopy (XPS) and Fourier-transform infrared spectroscopy (FTIR). Acellular oxidant generation was confirmed using electron paramagnetic resonance (EPR) spectroscopy (free radical detection), and ferrous reducing ability of serum (FRAS) assay. In vivo and in vitro oxidant generation were confirmed using EPR, flow cytometry, immuno spin-trapping (IST) and FRAS assay. Mouse macrophages (RAW264.7), and C57BL/6 mice were exposed to CBox and CB NPS at human relevant exposure concentrations (0-50 µg/mL in vitro and 20 µg/mouse oropharyngeal aspiration in vivo). Conditioned media from the CBox exposed macrophage cultures was used to treat mouse endothelial cells (C166). Compared with pristine CB, CBox demonstrated 2-4-fold greater potential to generate free radicals under acellular, cellular and in vivo conditions. Pharmacological inhibitor studies confirmed an oxidant/MAPK/NFkb dependent pro-inflammatory response (gene and protein expression of CXCL9, 10, 11, TNF-a, IL-6) in mice and in in vitro exposed macrophages. Conditioned media from CBox treated macrophage induced greater endothelial dysfunction (monolayer permeability and inhibition of wound healing). Pharmacological inhibition confirmed a C-X-C chemokine receptor 3-mediated pathway involvement in the CBox toxicity. In summary, this work clearly demonstrates biological potency of CBox and warrant further mechanistic studies on oxidized nanomaterials safety assessment. [Description provided by NIOSH]
• Subjects:
  Air Pollution Animals Blood Genetics Laboratories Macrophages Occupational Health Ozone Particulate Matter Safety
• Keywords:
  Oxidation; Particulates; Air pollution; Ozone; Nanoparticles; Macrophages; Endothelial cells; In vivo study; In vitro study; Animals; Laboratory animals; Proteins; Genes
• ISSN:
  1096-6080
• Document Type:
  Text
• Genre:
  Abstract or Summary
• Place as Subject:
  Massachusetts ; OSHA Region 1 ; 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
• Volume:
  186
• NIOSHTIC Number:
  nn:20064930
• Citation:
  Toxicologist 2022 Mar; 186(S1):225
• CAS Registry Number:
  Carbon black (CAS RN 1333-86-4) ; Ozone (CAS RN 10028-15-6)
• Federal Fiscal Year:
  2022
• NORA Priority Area:
  Construction ; Manufacturing
• Peer Reviewed:
  False
• Source Full Name:
  The Toxicologist. Society of Toxicology 61st Annual Meeting & ToxExpo, March 27-31, 2022, San Diego, California
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:053f7b1a7c6a98aba85c26c93c389475673eaeb3ff1c48f99777b667495613ee491c9b3d7a9016016d11f5d3399e2dfbcbe3be9f0e0312b4cfaeadd7174acbc0
• Download URL:
  https://stacks.cdc.gov/view/cdc/249279/cdc_249279_DS1.pdf
• File Type:
  [PDF - 224.12 KB ]