title: Multiwalled carbon nanotubes induce altered morphology and loss of barrier function in human bronchial epithelium at noncytotoxic doses.
abstract: Multiwalled carbon nanotubes (MWCNTs) have seen increasing application in consumer products over the past decade, resulting in an increasing risk of human exposure. While numerous toxicological studies have been performed using acute high doses of various carbonaceous nanomaterials, the effects of longer-term, low doses of MWCNTs remain relatively unexplored. This study examined bronchoscopy-derived healthy human bronchial epithelial cells exposed in submerged culture to noncytotoxic doses of MWCNTs over 7 days. Under these conditions, doses as low as 3 μg/mL caused altered cell morphology, superficially resembling fibroblasts. Electrical impedance of the epithelial monolayer was greatly reduced following MWCNT exposure. However, Western blot and polymerase chain reaction showed no elevated expression of the fibroblast markers, vimentin, α-smooth muscle actin, or fibronectin, indicating that a mechanism other than epithelial-mesenchymal transition may be responsible for the changes. Phalloidin and tubulin immunostaining showed disruption of the cytoskeleton, and confocal imaging showed a reduction of the tight junction proteins, zona occludens 1 and occludin. We propose that MWCNTs interfere with the cytoskeleton of the lung epithelium, which can result in a harmful reduction in barrier function over time, even at noncytotoxic doses.
authors.affiliation: Clinical Research Unit, National Institute of Environmental Health Sciences/National Institutes of Health, Research Triangle Park, NC, USA.
authors.forename: Ryan J
authors.initials: RJ
authors.lastname: Snyder
authors.affiliation: Clinical Research Unit, National Institute of Environmental Health Sciences/National Institutes of Health, Research Triangle Park, NC, USA.
authors.forename: Salik
authors.initials: S
authors.lastname: Hussain
authors.affiliation: Clinical Research Unit, National Institute of Environmental Health Sciences/National Institutes of Health, Research Triangle Park, NC, USA.
authors.forename: Annette B
authors.initials: AB
authors.lastname: Rice
authors.affiliation: Clinical Research Unit, National Institute of Environmental Health Sciences/National Institutes of Health, Research Triangle Park, NC, USA.
authors.forename: Stavros
authors.initials: S
authors.lastname: Garantziotis
mesh_terms: D001980:Bronchi / Q000166:cytology*; D016923:Cell Death / Q000187:drug effects; D048430:Cell Shape / Q000187:drug effects; D002478:Cells, Cultured; D003598:Cytoskeletal Proteins / Q000378:metabolism; D017097:Electric Impedance; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects; D006801:Humans; D037742:Nanotubes, Carbon / Q000737:chemistry / Q000633:toxicity*; D019108:Tight Junctions / Q000378:metabolism
chemical_list: D003598:Cytoskeletal Proteins; D037742:Nanotubes, Carbon
keywords: bronchial epithelium; cytoskeleton; human; morphology; multiwalled carbon nanotubes; transepithelial electrical resistance