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Potential in vitro model for testing the effect of exposure to nanoparticles on the lung alveolar epithelial barrier.

Authors
Derk-R; Davidson-DC; Manke-A; Stueckle-TA; Rojanasakul-Y; Wang-L
Source
Sens Bio-Sens Res 2015 Mar; 3:38-45
NIOSHTIC No.
20045529
Abstract
Pulmonary barrier function plays a pivotal role in protection from inhaled particles. However, some nano-scaled particles, such as carbon nanotubes (CNT), have demonstrated the ability to penetrate this barrier in animal models, resulting in an unusual, rapid interstitial fibrosis. To delineate the underlying mechanism and specific bio-effect of inhaled nanoparticles in respiratory toxicity, models of lung epithelial barriers are required that allow accurate representation of in vivo systems; however, there is currently a lack of consistent methods to do so. Thus, this work demonstrates a well-characterized in vitro model of pulmonary barrier function using Calu-3 cells, and provides the experimental conditions required for achieving tight junction complexes in cell culture, with trans-epithelial electrical resistance measurement used as a biosensor for proper barrier formation and integrity. The effects of cell number and serum constituents have been examined and we found that changes in each of these parameters can greatly affect barrier formation. Our data demonstrate that use of 5.0x104 Calu-3 cells/well in the Transwell cell culture system, with 10% serum concentrations in culture media is optimal for assessing epithelial barrier function. In addition, we have utilized CNT exposure to analyze the dose-, time-, and nanoparticle property- dependent alterations of epithelial barrier permeability as a means to validate this model. Such high throughput in vitro cell models of the epithelium could be used to predict the interaction of other nanoparticles with lung epithelial barriers to mimic respiratory behavior in vivo, thus providing essential tools and bio-sensing techniques that can be uniformly employed.
Keywords
Nanotechnology; Pulmonary-function; Pulmonary-system; Pulmonary-system-disorders; Particulate-dust; Particulates; Animals; Fibrosis; Toxins; Toxic-effects; Respiration; Models; Lung; In-vitro-studies; In-vivo-studies; Author Keywords: nanoparticles; lung; in vitro model; pulmonary barrier; toxicology
Contact
Liying Wang, MD/PhD, HELD/PPRB, National Institute for Occupational Safety and Health, 1095 Willowdale Road, Morgantown, WV, 26505
Publication Date
20150301
Document Type
Journal Article
Email Address
lmw6@cdc.gov
Fiscal Year
2015
NTIS Accession No.
NTIS Price
ISSN
2214-1804
NIOSH Division
HELD
Priority Area
Manufacturing
Source Name
Sensing and Bio-Sensing Research
State
WV
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