title: Cellular prion protein is expressed on endothelial cells and is released during apoptosis on membrane microparticles found in human plasma.
abstract: BACKGROUND
  Blood and plasma of animals experimentally infected with transmissible spongiform encephalopathies (TSEs) can transmit TSE infection by transfusion. A conformational isoform of prion protein (PrPsc) is believed to be the TSE-infectious agent that propagates by converting the cellular prion protein (PrPc) to additional molecules of PrPsc. In orally infected animals, PrPsc accumulates in intestinal endothelial cells. In blood, two thirds of PrPc resides in plasma, but its source is not known.
  
  
  METHODS
  The expression of PrPc in cultured human umbilical vein endothelial cells (HUVECs) was studied using flow cytometry, immunoblotting, and RT-PCR. Flow cytometry was used to characterize endothelial membrane microparticles (MPs) in cell culture supernatants and in normal human plasma.
  
  
  RESULTS
  HUVECs and bovine aorta endothelial cells express PrPc. The number of surface PrPc molecules per cell in HUVECs was 58,000 +/- 2,800. The induction of apoptosis in HUVECs led to a marked release of membrane MPs (60,000-80,000 MPs/10(3) cells) that expressed PrPc and other endothelial antigens. The presence of endothelial cell-derived MPs expressing PrPc was demonstrated in platelet-free human plasma.
  
  
  CONCLUSIONS
  Endothelial cell apoptosis is associated with the release of PrPc-positive MPs. These MPs contribute to the PrPc pool in plasma and may have a role in disseminating TSE infectivity in blood.
authors.affiliation: Laboratory of Cellular Hematology, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, Maryland 28092, USA.
authors.forename: Jan
authors.initials: J
authors.lastname: Simák
authors.forename: Karel
authors.initials: K
authors.lastname: Holada
authors.forename: Felice
authors.initials: F
authors.lastname: D'Agnillo
authors.forename: Jan
authors.initials: J
authors.lastname: Janota
authors.forename: Jaroslav G
authors.initials: JG
authors.lastname: Vostal
mesh_terms: D000818:Animals; D017304:Annexin A5 / Q000378:metabolism; D000911:Antibodies, Monoclonal; D001011:Aorta; D017209:Apoptosis / Q000187:drug effects; D001792:Blood Platelets / Q000648:ultrastructure; D002166:Camptothecin / Q000494:pharmacology; D002417:Cattle; D018929:Cell Culture Techniques; D002462:Cell Membrane / Q000378:metabolism*; D004591:Electrophoresis, Polyacrylamide Gel; D004730:Endothelium, Vascular / Q000378:metabolism* / Q000648:ultrastructure; D005434:Flow Cytometry; D006801:Humans; D015151:Immunoblotting; D007962:Leukocytes / Q000648:ultrastructure; D018621:PrPC Proteins / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D017096:Prion Diseases / Q000097:blood; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012756:Sheep; D014471:Umbilical Veins
chemical_list: D017304:Annexin A5; D000911:Antibodies, Monoclonal; D018621:PrPC Proteins; D012333:RNA, Messenger; D002166:Camptothecin