Details:

Alternative Title:
Part Fibre Toxicol
Personal Author:
Snyder-Talkington, Brandi N ; Schwegler-Berry, Diane ; Castranova, Vincent ; Qian, Yong ; Guo, Nancy L
Snyder-Talkington, Brandi N ; Schwegler-Berry, Diane ; Castranova, Vincent ; Qian, Yong ; Guo, Nancy L Less -
Description:
Background

Nanotechnology, particularly the use of multi-walled carbon nanotubes (MWCNT), is a rapidly growing discipline with implications for advancement in a variety of fields. A major route of exposure to MWCNT during both occupational and environmental contact is inhalation. While many studies showed adverse effects to the vascular endothelium upon MWCNT exposure, in vitro results often do not correlate with in vivo effects. This study aimed to determine if an alveolar-capillary co-culture model could determine changes in the vascular endothelium after epithelial exposure to MWCNT.

Methods

A co-culture system in which both human small airway epithelial cells and human microvascular endothelial cells were separated by a Transwell membrane so as to resemble an alveolar-capillary interaction was used. Following exposure of the epithelial layer to MWCNT, the effects to the endothelial barrier were determined.

Results

Exposure of the epithelial layer to MWCNT induced multiple changes in the endothelial cell barrier, including an increase in reactive oxygen species, actin rearrangement, loss of VE-cadherin at the cell surface, and an increase in endothelial angiogenic ability. Overall increases in secreted VEGFA, sICAM-1, and sVCAM-1 protein levels, as well as increases in intracellular phospho-NF-κB, phospho-Stat3, and phospho-p38 MAPK, were also noted in HMVEC after epithelial exposure.

Conclusion

The co-culture system identified that alveolar-capillary exposure to MWCNT induced multiple changes to the underlying endothelium, potentially through cell signaling mediators derived from MWCNT-exposed epithelial cells. Therefore, the co-culture system appears to be a relevant in vitro method to study the pulmonary toxicity of MWCNT.


Subjects:
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Actins Airway Epithelium Antigens, CD Blood-Air Barrier Cadherins Capillaries Capillary Permeability Co-culture Coculture Techniques Endothelial Cells Endothelium Humans Inflammation Mediators Intercellular Adhesion Molecule-1 MWCNT Nanotubes, Carbon Neovascularization, Pathologic NF-kappa B P38 Mitogen-Activated Protein Kinases Phosphorylation Pneumocytes Pulmonary Fibrosis Pulmonary Inflammation Reactive Oxygen Species Research Respiratory Mucosa STAT3 Transcription Factor Time Factors Vascular Cell Adhesion Molecule-1 Vascular Endothelial Growth Factor A
Source:
Part Fibre Toxicol. 2013; 10:35.
Document Type:
Journal Article
Collection(s):
CDC Public Access
Main Document Checksum:
[+]
urn:sha256:9ae46757f76fadab13c124c97b9de11e131f05a5977fc57cf6a96d63072ea33b
Download URL:
https://stacks.cdc.gov/view/cdc/21077/cdc_21077_DS1.pdf
File Type:

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