Time-Course Relationships Between Airway Inflammation, Circulating Exosome Formation, and Systemic Vascular Responses Following Pulmonary Multiwall Carbon Nanotube Exposures

Details

• Personal Author:
  Campen M ; Erdely A ; Herbert G ; Lucas S ; Ottens A ; Sanchez B ; Young TL
• Description:
  We previously reported that short-term MWCNT exposure produces serum bioactivity that impairs endothelial function leading to vasodilatory insufficiencies, as well as induction of blood-brain barrier (BBB) impairments. The mechanisms underlying observed systemic effects are incompletely understood and the contribution of extracellular vesicles, or exosomes, to the systemic delivery of lung-derived inflammatory mediators was explored in this study. We hypothesized that the systemic effects of MWCNT were mediated via exosomal delivery of pulmonary-derived bioactivity in serum. To test this hypothesis, male wild-type C57BL/6 mice (6-8 weeks) exposed to 0 (dispersion media; DM), 3 or 10 microg MWCNT via oropharyngeal aspiration were euthanized at 1, 3 or 7 days post-exposure. Bronchoalveolar lavage fluid (BALF), serum and tissues were collected. Inflammatory cytokine/chemokine expression in BALF was determined by electrochemiluminescence. Serum bioactivity (with and without exosomal fractions) was assessed via 1) serum cumulative inflammatory potential (SCIP) assay on mouse brain endothelial cells (MBEC) and 2) myography using naïve thoracic aorta from male C57BL6 mice incubated with 1% serum from exposed mice to evaluate vasodilatory changes. Analyses of BALF inflammatory cytokines revealed dose- and time-dependent increases in IL-1beta, IL-4, IL-5, TNF-alpha and KC/GRO. Maximal neutrophil influx was observed 1d following the 3 microg dose, but at 3d following the 10 microg dose. A significant increase in TNF-alpha gene expression was observed with serum containing the exosomal fraction when compared with exosome depleted fractions and DM controls. No significant BBB changes were observed using sodium fluorescein cerebral uptake assay. Further evaluations of BBB integrity will be done via immunohistochemistry. Evaluation of other systemic parameters are ongoing. These preliminary findings suggest that MWCNT pulmonary exposure induces inflammatory activation in the lungs of C57BL6 mice in a dose- and time-dependent manner and may produce serum bioactivity via exosomal delivery. [Description provided by NIOSH]
• Subjects:
  Biological Assay Blood Body Fluids Cells, Cultured Environmental Exposure Immune System Laboratories Lung Occupational Health Respiratory System Safety Toxicology

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• Keywords:
  Bioactivation Bioassays Blood Cells Blood Serum Body Fluids Brain Matter Carbon Nanotubes Cell Cultures Chemiluminescence Immunoassay Cytokines Dose Response Electrochemical Analysis Endothelial Cells Exposure Assessment Exposure Levels Gene Expression Immune Reaction Laboratory Animals Laboratory Testing Lung Irritants Lung Tissue Multi-walled Carbon Nanotubes MWCNT Nanotechnology Nanotoxicology Neutrophils Tissue Culture Toxic Effects Vasomotor System

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• ISSN:
  1096-6080
• Document Type:
  Text
• Funding:
  Grant
• Genre:
  Abstract or Summary
• Place as Subject:
  New Mexico ; OSHA Region 3 ; OSHA Region 6 ; Texas ; 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:
  162
• Issue:
  1
• NIOSHTIC Number:
  nn:20051254
• Citation:
  Toxicologist 2018 Mar; 162(1):415
• 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:
  The Toxicologist. Society of Toxicology 57th Annual Meeting and ToxExpo, March 11-15, 2018, San Antonio, Texas
• End Date:
  20190929
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:043d91f4128cdf715e829a360af27fc09a498ff1a01e450c55e8d2bdb760ac244328c7e1e0a12599742d2db1238e4cba2ae12fd70da41a5ab5c7c87f435bc945
• Download URL:
  https://stacks.cdc.gov/view/cdc/211317/cdc_211317_DS1.pdf
• File Type:
  [PDF - 839.53 KB ]