title: Multi-walled carbon nanotubes induce human microvascular endothelial cellular effects in an alveolar-capillary co-culture with small airway epithelial cells.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Pathology and Physiology Research Branch, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, 1095 Willowdale Road, Morgantown, WV 26505-2888, USA.
authors.forename: Brandi N
authors.initials: BN
authors.lastname: Snyder-Talkington
authors.forename: Diane
authors.initials: D
authors.lastname: Schwegler-Berry
authors.forename: Vincent
authors.initials: V
authors.lastname: Castranova
authors.forename: Yong
authors.initials: Y
authors.lastname: Qian
authors.forename: Nancy L
authors.initials: NL
authors.lastname: Guo
mesh_terms: D000199:Actins / Q000378:metabolism; D056809:Alveolar Epithelial Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D015703:Antigens, CD / Q000378:metabolism; D015824:Blood-Air Barrier / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D015820:Cadherins / Q000378:metabolism; D002196:Capillaries / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D002199:Capillary Permeability / Q000187:drug effects; D018920:Coculture Techniques; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D037742:Nanotubes, Carbon / Q000633:toxicity*; D009389:Neovascularization, Pathologic; D010766:Phosphorylation; D017382:Reactive Oxygen Species / Q000378:metabolism; D020545:Respiratory Mucosa / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D050796:STAT3 Transcription Factor / Q000378:metabolism; D013997:Time Factors; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism; D000099152:Cadherin 5
chemical_list: D000199:Actins; D015703:Antigens, CD; D015820:Cadherins; D018836:Inflammation Mediators; D018799:Intercellular Adhesion Molecule-1; D016328:NF-kappa B; D037742:Nanotubes, Carbon; D017382:Reactive Oxygen Species; D050796:STAT3 Transcription Factor; D019010:Vascular Cell Adhesion Molecule-1; D042461:Vascular Endothelial Growth Factor A; D048051:p38 Mitogen-Activated Protein Kinases; D000099152:Cadherin 5; C573420:ICAM1 protein, human; C494086:STAT3 protein, human; C467484:VEGFA protein, human
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