Functional assessment of the serome following pulmonary exposure to carbon nanotubes

Details

• Personal Author:
  Aragon M ; Campen M ; Erdely A ; Ottens AK
• Description:
  Assessing the mechanisms underlying adverse cardiovascular effects induced by inhaled toxins presents a substantial research challenge. We propose that blood carries an as yet unknown "inflammatory potential" consisting of modified proteins or other biomolecules and reaction byproducts that affects a pathological bioactivity which can be assessed using endothelial cells as biosensors. The approach involves applying serum from exposed animals to cultured primary endothelial cells or ex vivo isolated arteries. Mice were exposed to multi-walled carbon nanotubes (MWCNT; 0, 10 or 40 ug) via pharyngeal aspiration and serum was collected at 4 and 24 h post-exposure. Serum from exposed mice increased endothelial cell surface vascular cell adhesion molecule-1 (VCAM-1) and intracellular adhesion molecule-1 (ICAM-1) expression and proinflammatory transcripts, and decreased ATP-stimulated nitric oxide (NO) production. The functional impact of this loss of NO bioavailability was confirmed via myography, in which serum from MWCNT-exposed mice significantly impaired vasodilation to acetylcholine. In addition, serum from MWCNT-exposed mice reduced cell migration in a traditional scratch assay experiment. To identify the bioactive circulating components in the serum, a data-independent 'omic platform enabled reproducible label-free quantitative analysis revealed a diverse set of serum factors in the size range of 500- 5000 Da altered due to MWCNT exposure. Each dose was associated with its own independent set of selective factors that differentiated the two MWCNT exposure groups. More compelling was that this particular size fraction had functional effects on endothelial cell function. In conclusion, pulmonary exposure to MWCNT dynamically alters circulating factors, which promotes endothelial cell activation, decreased NO bioavailability, and altered functionality all directionally predicting adverse cardiovascular outcomes. [Description provided by NIOSH]
• Subjects:
  Animals Cardiovascular System Laboratories Occupational Health Safety Toxicology
• Keywords:
  Animal-studies Carbon-compounds Cardiovascular-system Laboratory-animals Nanotechnology
• ISSN:
  1096-6080
• Document Type:
  Text
• Genre:
  Abstract or Summary
• Place as Subject:
  California ; New Mexico ; OSHA Region 3 ; OSHA Region 6 ; OSHA Region 9 ; Virginia ; 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:
  144
• Issue:
  1
• NIOSHTIC Number:
  nn:20045998
• Citation:
  Toxicologist 2015 Mar; 144(1):506
• CAS Registry Number:
  Carbon (CAS RN 7440-44-0)
• Federal Fiscal Year:
  2015
• NORA Priority Area:
  Manufacturing
• Peer Reviewed:
  False
• Source Full Name:
  The Toxicologist. Society of Toxicology 54th Annual Meeting and ToxExpo, March 22-26, 2015, San Diego, California
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:984d96b993a5b1851074d23347023272fc7c332af34f2660385a492c81020ea85427303879e6ddbcebce00cdd33d1b116bd23470e10b354a22616d523ffbf7c9
• Download URL:
  https://stacks.cdc.gov/view/cdc/201196/cdc_201196_DS1.pdf
• File Type:
  [PDF - 220.06 KB ]