Microvascular Dysfunction Following Multiwalled Carbon Nanotube Exposure Is Mediated by Thrombospondin-1 Receptor CD47

Details

• Personal Author:
  Kelley EE ; Mandler WK ; Nurkiewicz TR ; Olfert IM ; Porter DW
• Description:
  Pulmonary exposure to multi-walled carbon nanotubes (MWCNT) disrupts peripheral microvascular function. Thrombospondin-1 (TSP-1) is highly expressed during lung injury and has been shown to alter microvascular reactivity. It is unclear exactly how TSP-1 exerts effects on vascular function, but we hypothesized that the TSP-1 receptor CD47 may mediate changes in vasodilation. Wildtype (WT) or CD47 knockout (CD47 KO) C57B6/J-background animals were exposed to 50 µg of MWCNT or saline control via pharyngeal aspiration. Twenty-four hours post-exposure, intravital microscopy was performed to assess arteriolar dilation and venular leukocyte adhesion and rolling. To assess tissue redox status, electron paramagnetic resonance and NOx measurements were performed, while inflammatory biomarkers were measured via multiplex assay. Vasodilation was impaired in the WT+ MWCNT group compared to control (57 +/- 9% vs 90 +/- 2% relaxation), while CD47 KO animals showed no impairment (108 +/- 8% relaxation). Venular leukocyte adhesion and rolling increased by > 2-fold, while the CD47 KO group showed no change. Application of the antioxidant apocynin rescued normal leukocyte activity in the WT+ MWCNT group. Lung and plasma NOx were reduced in the WT+ MWCNT group by 47% and 32%, respectively, while the CD47 KO groups were unchanged from control. Some inflammatory cytokines were increased in the CD47+ MWCNT group only. In conclusion, TSP-1 is an important ligand mediating MWCNT-induced microvascular dysfunction, and CD47 is a component of this dysregulation. CD47 activation likely disrupts nitric oxide (.NO) signaling and promotes leukocyte-endothelial interactions. Impaired .NO production, signaling, and bioavailability is linked to a variety of cardiovascular diseases in which TSP-1/CD47 may play an important role. [Description provided by NIOSH]
• Subjects:
  Antioxidants Biological Assay Biomarkers Blood Cardiovascular Diseases Cardiovascular System Environmental Exposure Immune System Laboratories Lung Microbiology Musculoskeletal System Nitric Oxide Occupational Health Respiratory System Safety Toxicology

  More +
• Keywords:
  Author Keywords: Endothelial Dysfunction Bioassays Blood Vessels Carbon Nanotubes Cardiovascular Function Cardiovascular System Disorders Cytokines Endothelial Cells Exposure Assessment Exposure Levels Immune Reaction Laboratory Animals Laboratory Testing Leukocytes Lung Burden Microscopic Analysis Multi-walled Carbon Nanotubes Muscle Tissue MWCNT Nanomaterials Nanotechnology Nanotoxicology Nanotubes Nitric Oxide Nitrogen Oxides Oxidative Stress Proteins Pulmonary Exposure Pulmonary System Skeletal System Tissue Disorders Vasoactive Agents

  More +
• ISSN:
  1096-6080
• 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:
  90-99
• Volume:
  165
• Issue:
  1
• NIOSHTIC Number:
  nn:20051681
• Citation:
  Toxicol Sci 2018 Sep; 165(1):90-99
• Contact Point Address:
  Ivan Mark Olfert, West Virginia University School of Medicine, One Medical Center Drive, PO Box 9227, Morgantown, WV 26506
• Email:
  imolfert@hsc.wvu.edu
• CAS Registry Number:
  Acetovanillone (CAS RN 498-02-2) ; Carbon nanotubes (CAS RN 308068-56-6) ; Nitric oxide (CAS RN 10102-43-9) ; Nitrogen dioxide (CAS RN 10102-44-0)
• Federal Fiscal Year:
  2018
• NORA Priority Area:
  Manufacturing
• Peer Reviewed:
  True
• Source Full Name:
  Toxicological Sciences
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:1408518d079b02b7768d25a99d910b287f99152471315ed7ca3a9362fb6d77bdfc711eea343b89165ec4594fe9f7af2725fd951a5371fbda9807a0201ebd1b28
• Download URL:
  https://stacks.cdc.gov/view/cdc/211506/cdc_211506_DS1.pdf
• File Type:
  [PDF - 523.95 KB ]