title: Induction of inflammation in vascular endothelial cells by metal oxide nanoparticles: effect of particle composition.
abstract: BACKGROUND
  The mechanisms governing the correlation between exposure to ultrafine particles and the increased incidence of cardiovascular disease remain unknown. Ultrafine particles appear to cross the pulmonary epithelial barrier into the bloodstream, raising the possibility of direct contact with the vascular endothelium.
  
  
  OBJECTIVE
  Because endothelial inflammation is critical for the development of cardiovascular pathology, we hypothesized that direct exposure of human aortic endothelial cells (HAECs) to ultrafine particles induces an inflammatory response and that this response depends on particle composition.
  
  
  METHODS
  To test the hypothesis, we incubated HAECs for 1-8 hr with different concentrations (0.001-50 mug/mL) of iron oxide (Fe(2)O(3)), yttrium oxide (Y(2)O(3)), and zinc oxide (ZnO) nanoparticles and subsequently measured mRNA and protein levels of the three inflammatory markers intra-cellular cell adhesion molecule-1, interleukin-8, and monocyte chemotactic protein-1. We also determined nanoparticle interactions with HAECs using inductively coupled plasma mass spectrometry and transmission electron microscopy.
  
  
  RESULTS
  Our data indicate that nanoparticle delivery to the HAEC surface and uptake within the cells correlate directly with particle concentration in the cell culture medium. All three types of nanoparticles are internalized into HAECs and are often found within intracellular vesicles. Fe(2)O(3) nanoparticles fail to provoke an inflammatory response in HAECs at any of the concentrations tested; however, Y(2)O(3) and ZnO nanoparticles elicit a pronounced inflammatory response above a threshold concentration of 10 mug/mL. At the highest concentration, ZnO nanoparticles are cytotoxic and lead to considerable cell death.
  
  
  CONCLUSIONS
  These results demonstrate that inflammation in HAECs following acute exposure to metal oxide nanoparticles depends on particle composition.
authors: Department of Mechanical and Aeronautical Engineering, University of California, Davis, Davis, California, USA.
authors: Andrea
authors: A
authors: Gojova
authors: Bing
authors: B
authors: Guo
authors: Rama S
authors: RS
authors: Kota
authors: John C
authors: JC
authors: Rutledge
authors: Ian M
authors: IM
authors: Kennedy
authors: Abdul I
authors: AI
authors: Barakat
mesh_terms: D001011:Aorta / Q000166:cytology; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000096:biosynthesis / Q000235:genetics; D042783:Endothelial Cells / Q000187:drug effects* / Q000473:pathology; D005290:Ferric Compounds / Q000633:toxicity; D006801:Humans; D007249:Inflammation / Q000139:chemically induced* / Q000378:metabolism; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis / Q000235:genetics; D016209:Interleukin-8 / Q000235:genetics; D046529:Microscopy, Electron, Transmission; D053758:Nanoparticles / Q000633:toxicity* / Q000648:ultrastructure; D012333:RNA, Messenger / Q000096:biosynthesis; D015854:Up-Regulation; D015019:Yttrium / Q000633:toxicity*; D015034:Zinc Oxide / Q000633:toxicity*
chemical_list: C111835:CCL2 protein, human; D018932:Chemokine CCL2; D005290:Ferric Compounds; D016209:Interleukin-8; D012333:RNA, Messenger; D018799:Intercellular Adhesion Molecule-1; C000499:ferric oxide; D015019:Yttrium; D015034:Zinc Oxide; C091417:yttria