Macrophage Sensing of Single-Walled Carbon Nanotubes via Toll-Like Receptors

Details

• Personal Author:
  Andón FT ; Autio R ; Bondarenko O ; Bottini M ; Brzicová T ; Calligari P ; Fadeel B ; Gessner I ; Kisin E ; Kohonen P ; Lahesmaa R ; Mathur S ; Mukherjee SP ; Salminen-Mankonen H ; Shvedova A ; Stella L
• Description:
  Carbon-based nanomaterials including carbon nanotubes (CNTs) have been shown to trigger inflammation. However, how these materials are 'sensed' by immune cells is not known. Here we compared the effects of two carbon-based nanomaterials, single-walled CNTs (SWCNTs) and graphene oxide (GO), on primary human monocyte-derived macrophages. Genome-wide transcriptomics assessment was performed at sub-cytotoxic doses. Pathway analysis of the microarray data revealed pronounced effects on chemokine-encoding genes in macrophages exposed to SWCNTs, but not in response to GO, and these results were validated by multiplex array-based cytokine and chemokine profiling. Conditioned medium from SWCNT-exposed cells acted as a chemoattractant for dendritic cells. Chemokine secretion was reduced upon inhibition of NF-kappaB, as predicted by upstream regulator analysis of the transcriptomics data, and Toll-like receptors (TLRs) and their adaptor molecule, MyD88 were shown to be important for CCL5 secretion. Moreover, a specific role for TLR2/4 was confirmed by using reporter cell lines. Computational studies to elucidate how SWCNTs may interact with TLR4 in the absence of a protein corona suggested that binding is guided mainly by hydrophobic interactions. Taken together, these results imply that CNTs may be 'sensed' as pathogens by immune cells. [Description provided by NIOSH]
• Subjects:
  Blood Cytotoxins Genetics Immune System Macrophages Microbiology Occupational Health Safety Toxicology
• Keywords:
  Carbon Nanotubes Cell Signaling Cellular Effects Cellular Reactions Cytokines Cytotoxicity Dose Response Exposure Assessment Genes Genomics Graphene Graphene Oxide Immune Reaction Immune System Microorganisms Nanomaterials Nanotechnology Nanotoxicology Nanotubes Oxides Pathogens Proteins Single-walled Carbon Nanotubes SWCNT

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• ISSN:
  2045-2322
• Document Type:
  Text
• Genre:
  Journal Article
• Place as Subject:
  California ; OSHA Region 3 ; OSHA Region 9 ; 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:
  8
• NIOSHTIC Number:
  nn:20050859
• Citation:
  Sci Rep 2018 Jan; 8:1115
• Contact Point Address:
  Bengt Fadeel, Nanosafety & Nanomedicine Laboratory, Division of Molecular Toxicology, Institute of Environmental Medicine, Karolinska Institutet, 17177, Stockholm, Sweden
• Email:
  Bengt.Fadeel@ki.se
• CAS Registry Number:
  Carbon nanotubes (CAS RN 308068-56-6) ; Graphene (CAS RN 1034343-98-0)
• Federal Fiscal Year:
  2018
• NORA Priority Area:
  Manufacturing
• Peer Reviewed:
  True
• Source Full Name:
  Scientific Reports
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:70956495e2df3f11c6aef2d04d4f75a75c9a900afd97b9417a4c60a6f1f2c28096a2545937d750612f12f87bfed6719e9e31c55a9284cf74c7a5ecde1f7a051a
• Download URL:
  https://stacks.cdc.gov/view/cdc/211056/cdc_211056_DS1.pdf
• File Type:
  [PDF - 2.20 MB ]