title: The acute exposure effects of inhaled nickel nanoparticles on murine endothelial progenitor cells.
abstract: BACKGROUND
  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/m(3) 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.
  
  
  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.
authors.affiliation: Department of Environmental Medicine, New York University School of Medicine , Tuxedo, NY , USA and.
authors.forename: Eric N
authors.initials: EN
authors.lastname: Liberda
authors.forename: Azita K
authors.initials: AK
authors.lastname: Cuevas
authors.forename: Qingshan
authors.initials: Q
authors.lastname: Qu
authors.forename: Lung Chi
authors.initials: LC
authors.lastname: Chen
mesh_terms: D000818:Animals; D018929:Cell Culture Techniques; D049109:Cell Proliferation / Q000187:drug effects; D054377:Chemokine CXCL12 / Q000097:blood; D002633:Chemotaxis / Q000187:drug effects; D066026:Endothelial Progenitor Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects*; D005434:Flow Cytometry; D019570:Inhalation Exposure / Q000009:adverse effects*; D008297:Male; D053768:Metal Nanoparticles / Q000737:chemistry / Q000633:toxicity*; D008810:Mice, Inbred C57BL; D009532:Nickel / Q000737:chemistry / Q000633:toxicity*; D010316:Particle Size; D020543:Proteome / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D042461:Vascular Endothelial Growth Factor A / Q000097:blood
chemical_list: D054377:Chemokine CXCL12; D020543:Proteome; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; D009532:Nickel
keywords: Endothelial progenitor cells; inhalation; nanoparticles; nickel