Hunting Circulating Mediators of Systemic Vascular Dysfunction After Carbon Nanotube Exposure

Details

• Personal Author:
  Ottens A
• Description:
  Engineered carbon nanomaterials are growing in diversity and popularity for manufacturing strong, lightweight components. Yet, health risk assessments on these materials have only recently begun. Concern over their small size and ease with which they disperse and become trapped within the lung raises questions over their pulmonary as well as extrapulmonary health effects. Recent studies have demonstrated functional consequences outside the lung, and in particular on the vasculature. Blood from exposed animals can cause inflammation and dysfunction in naïve cells and tissues, yet the carbon nanotube material itself is restricted principally to the lung. Studies are ongoing to assess factors introduced into circulation that contribute to systemic health consequences, such as disruption of the blood-brain barrier and induced neuroinflammation. Male C57BL/6 mice were exposed to two doses of multi-walled carbon nanotubes (Matsui-7, 49 nm mean diameter) or vehicle (n=6/group). Samples were size fractionated and assessed using label-free data independent analysis. Mass spectrometry revealed over 1,700 circulating factors significantly altered by nanotube exposure that correlated with levels present within bronchial lavage fluid. Lung tissue showed significant 2-fold or greater increases in 12 matrix proteases supporting a pulmonary origin of peptide proteolytic products released into circulation. Peptide analysis identified products from known matrix protease substrates and secretory proteins, which offered functional relevance to immunoinflammatory responses, extracellular matrix remodeling, and receptor interactions. The tested fraction was further evaluated and found to induce inflammatory marker release in naïve endothelial cells as well as vasodilatory dysfunction in naïve blood vessels. Of particular interest was a 58-mer thrombospondin fragment that contains antiangiogenic CD36 binding characteristics as needed to induce the observed vascular dysfunction. Results from these studies underlie an indirect mechanism by which pulmonary insults, such as to nanomaterials, can translate into systemic health consequences. [Description provided by NIOSH]
• Subjects:
  Animals Lung Occupational Health Respiratory System Safety Toxicology
• Keywords:
  Animal Studies Health Effects Multi-walled Carbon Nanotubes MWCNT Nanomaterials Pulmonary Effects
• Publisher:
  US HUPO (US Human Proteome Organization)
• Document Type:
  Text
• Funding:
  Grant
• Genre:
  Abstract or Summary
• Place as Subject:
  New Mexico ; OSHA Region 3 ; OSHA Region 6 ; Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  24-25
• NIOSHTIC Number:
  nn:20063341
• Citation:
  US HUPO 2018: 14th Annual Conference of the US Human Proteome Organization, March 11-14, 2018, Minneapolis, Minnesota. Portland, OR: US HUPO (US Human Proteome Organization), 2018 Mar; :24-25
• CAS Registry Number:
  Carbon nanotubes (CAS RN 308068-56-6)
• Federal Fiscal Year:
  2018
• NORA Priority Area:
  Manufacturing
• Performing Organization:
  University of New Mexico Health Sciences Center, Albuquerque, New Mexico
• Peer Reviewed:
  False
• Start Date:
  20150930
• Source Full Name:
  US HUPO 2018: 14th Annual Conference of the US Human Proteome Organization, March 11-14, 2018, Minneapolis, Minnesota
• End Date:
  20190929
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:5d978e59c4fa9617b4493a254727ef956afafa9bf09f1da2068b81f48c3a2e33ff985a4dbf4860ced4c5342070a83d781e2abddb7d862d9c1543b5c1f7264771
• Download URL:
  https://stacks.cdc.gov/view/cdc/226420/cdc_226420_DS1.pdf
• File Type:
  [PDF - 212.91 KB ]