The acute exposure effects of inhaled nickel nanoparticles on murine endothelial progenitor cells

Eric N. Liberdaab, Azita K. Cuevasa, Qingshan Qua & Lung Chi Chen*aa Department of Environmental Medicine, New York University School of Medicine Tuxedo, NYUSAb School of Occupational and Public Health, Ryerson University OntarioCanadaAddress for correspondence: Lung Chi Chen, PhDDepartment of Environmental Medicine, New York University School of Medicine 57 Old Forge Road, Tuxedo, NY 10987USA. E-mail: lung-chi.chen@nyumc.orgAbstractIntroduction: The discovery of endothelial progenitor cells (EPCs) may help to explain observed cardiovascular effects associated with inhaled nickel nanoparticle exposures, such as increases in vascular inflammation, generation of reactive oxygen species, altered vasomotor tone and potentiated atherosclerosis in murine species.Methods: Following an acute whole body inhalation exposure to 500 µg/m3 of nickel nanoparticles for 5 h, bone marrow EPCs from C57BL/6 mice were isolated. EPCs were harvested for their RNA or used in a variety of assays including chemotaxis, tube formation and proliferation. Gene expression was assessed for important receptors involved in EPC mobilization and homing using RT-PCR methods. EPCs, circulating endothelial progenitor cells (CEPCs), circulating endothelial cells (CECs) and endothelial microparticles (EMPs) were quantified on a BD FACSCalibur to examine endothelial damage and repair associated with the exposure.Results and conclusions: Acute exposure to inhaled nickel nanoparticles significantly increased both bone marrow EPCs as well as their levels in circulation (CEPCs). CECs were significantly elevated indicating that endothelial damage occurred due to the exposure. There was no significant difference in EMPs between the two groups. Tube formation and chemotaxis, but not proliferation, of bone marrow EPCs was impaired in the nickel nanoparticle exposed group. These results coincided with a decrease in the mRNA of receptors involved in EPC mobilization and homing. These data provide new insight into how an acute nickel nanoparticle exposure to half of the current Occupational Safety & Health Administration (OSHA) permissible exposure limit may adversely affect EPCs and exacerbate cardiovascular disease states.