Induction of Inflammation in Vascular Endothelial Cells by Metal Oxide Nanoparticles: Effect of Particle Composition Andrea Gojova,1 Bing Guo,2 Rama S. Kota,3 John C. Rutledge,3 Ian M. Kennedy,1 and Abdul I. Barakat1 1Department of Mechanical and Aeronautical Engineering, University of California, Davis, Davis, California, USA; 2Department of Mechanical Engineering, Texas A&M University, College Station, Texas, USA; 3Department of Internal Medicine, University of California, Davis, Davis, California, USA 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. Objectives: 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 µg/mL) of iron oxide (Fe2O3) , yttrium oxide (Y2O3) , and zinc oxide (ZnO) nanoparticles and subsequently measured mRNA and protein levels of the three inflammatory markers intracellular 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. Fe2O3 nanoparticles fail to provoke an inflammatory response in HAECs at any of the concentrations tested ; however, Y2O3 and ZnO nanoparticles elicit a pronounced inflammatory response above a threshold concentration of 10 µg/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. Key words: air pollution, atherosclerosis, cardiovascular disease, endothelial cells, inflammation, nanoparticles, particulate matter. Environ Health Perspect 115:403–409 (2007) . doi:10.1289/ehp.8497 available via http://dx.doi.org/ [Online 11 December 2006] Address correspondence to A.I. Barakat, Department of Mechanical and Aeronautical Engineering, University of California, Davis, One Shields Ave., Davis, CA 95616 USA. Telepone: (530) 754-9295. Fax: (530) 752-4158. E-mail: abarakat@ucdavis.edu We thank G. Adamson, P. Kysar, and X. Feng for electron microscopy ; R. Shiraki for ICP-MS analyses ; A. Navrotsky, J. Neil, and S. Ushakov for use of XRD and BET instruments and related technical assistance. This study was supported in part by grant DBI-0102662 from the National Science Foundation ; Superfund Basic Research Program grant 5P42ES04699 from the National Institute of Environmental Health Sciences (NIEHS) , National Institutes of Health (NIH) ; grant P30-ES05705 from the NIEHS ; and grant HL55667 from the National Heart, Lung, and Blood Institute, NIH. Research described in this article was also conducted under contract to the Health Effects Institute (HEI) , an organization jointly funded by the U.S. Environmental Protection Agency (EPA) (Assistance Agreement R82811201) and automotive manufacturers. The contents of this article do not necessarily reflect the views of HEI, nor do they necessarily reflect the views and policies of EPA or of motor vehicle and engine manufacturers. The authors declare they have no competing financial interests. Received 13 July 2006 ; accepted 11 December 2006. The full version of this article is available for free in HTML or PDF formats. |