Induction of serum inflammatory potential by pulmonary exposure to multi-walled carbon nanotubes

Details

• Personal Author:
  Aragon M ; Campen MJ ; Erdely A
• Description:
  It has become widely acknowledged that a pulmonary particulate exposure has adverse effects beyond the lungs and can exert an important influence on the cardiovascular system, but pathological mechanisms to explain extrapulmonary insult remain unclear. We propose that serum carries an as yet unknown "inflammatory potential", possibly consisting of degradation byproducts, adducted or modified endogenous proteins, or other modified components, that affects a pathological bioactivity which can be assessed using endothelial cells as biosensors. To confirm the phenomenon of serum inflammatory potential related to nanoparticulate exposures, we characterized a number of responses induced by serum from mice exposed to MWCNTs by pulmonary aspiration (0, 10, 40 ug/mouse) and inhalation (5 h/d x 19 d of 0.05, 0.5, and 5.0 mg/m3), with serum collected 4h and 24h after exposures. Primary mouse cerebrovascular endothelial cells treated with serum from exposed mice showed consistent elevation of adhesion molecules ICAM and VCAM, both in terms of relative mRNA and cell surface expression. Additionally, genomic assessment of treated endothelial cells revealed a panel of Toll-like receptor- and NF-kappaB-related responses upregulated, relative to cells treated with serum from control mice. Cell growth and proliferation pathways were downregulated, which mirrored functional outcomes of an in vitro scratch assay. Serum from MWCNT exposed mice also impaired ATP-stimulated endothelial nitric oxide synthesis, as measured by spin-trap electron paramagnetic resonance. Findings from aspiration studies were generally supported by results from sub-chronic inhalation exposures. These outcomes indicate the presence of pathological bioactive constituents in the serum following exposure to MWCNTs. The nature of these components remains unclear, but conventional inflammatory cytokines do not appear to be primary regulators. Future research to characterize the complete chemical and biological mixture of serum, linked to adverse bioactivity, is needed to better understand the extrapulmonary effects of inhaled toxicants. The findings of bioactivity in the serum may help explain many extrapulmonary outcomes related to inhaled nanoparticles and other toxicants. [Description provided by NIOSH]
• Subjects:
  Animals Cardiovascular System Hazardous Substances Laboratories Lung Lung Diseases Occupational Health Particulate Matter Pathology Respiratory System Respiratory Tract Diseases Risk Assessment Risk Factors Safety

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• Keywords:
  Cardiovascular-system Cell-function Cellular-function Exposure-levels Laboratory-animals Lung-disorders Lung-function Nanotechnology Particulates Pathogens Proteins Pulmonary-function Pulmonary-system Pulmonary-system-disorders Respiratory-system-disorders Risk-factors Toxins

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• ISSN:
  1073-449X
• Document Type:
  Text
• Funding:
  Grant
• Genre:
  Abstract or Summary
• Place as Subject:
  New Mexico ; OSHA Region 3 ; OSHA Region 6 ; 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:
  189
• NIOSHTIC Number:
  nn:20045271
• Citation:
  Am J Respir Crit Care Med 2014 May; 189(Meeting Abstracts):A3808
• CAS Registry Number:
  Nitric oxide (CAS RN 10102-43-9)
• Federal Fiscal Year:
  2014
• NORA Priority Area:
  Manufacturing
• Performing Organization:
  University of New Mexico Health Sciences Center, Albuquerque, New Mexico
• Peer Reviewed:
  False
• Start Date:
  20130901
• Source Full Name:
  American Journal of Respiratory and Critical Care Medicine
• Supplement:
  Meeting Abstracts
• End Date:
  20150831
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:3e3416c2df2cbcbb31ed33615a98047b0461f964981d76b056e504f67e08a48ec562d19d30caa07f9afc1bec48e7602aa995a9c75399407f8fddae0d2695ed64
• Download URL:
  https://stacks.cdc.gov/view/cdc/200739/cdc_200739_DS1.pdf
• File Type:
  [PDF - 21.24 KB ]