title: The expression of prion protein by endothelial cells: a source of the plasma form of prion protein?
abstract: The neuronal prion protein (PrPC) is also expressed within peripheral tissues including human blood. The majority of blood PrPC is found within the plasma fraction. We hypothesized that the vascular endothelium could be a source of this PrPC. Reverse transcription polymerase chain reaction demonstrated that both human umbilical vein endothelial cells (HUVEC) and human microvascular endothelial cells (HMEC-1) expressed PrPC mRNA. Flow cytometry confirmed PrPC expression on HMEC-1s and HUVECs (120900 +/- 15058 and 58327 +/- 4577 molecules PrPC/cell respectively), with no upregulation following cellular activation. Confocal immunofluorescence microscopy confirmed that HMEC-1s and HUVECs were positive for PrPC on the plasma membrane. Time-resolved dissociation-enhanced fluoroimmunoassay (DELFIA) analysis of cell culture medium demonstrated a slow constitutive release of soluble PrPC not associated with activation. In contrast to von Willebrand factor antigen, PrPC plasma levels in vivo decrease following desmopressin therapy in patients with von Willebrand disease. Measurement of PrPC plasma levels in patients with varying blood counts demonstrated no association between cell count and PrPC concentration. However, there was a higher level of PrPC in plasma from patients with end-stage renal failure. In conclusion, endothelial cells of both macrovascular and microvascular origin expressed high levels of PrPC which can be constitutively released into the cell culture medium.
authors.affiliation: Haemostasis Research Unit, Department of Haematology, University College London, UK. r.starke@ucl.ac.uk
authors.forename: Richard
authors.initials: R
authors.lastname: Starke
authors.forename: Olive
authors.initials: O
authors.lastname: Drummond
authors.forename: Ian
authors.initials: I
authors.lastname: MacGregor
authors.forename: John
authors.initials: J
authors.lastname: Biggerstaff
authors.forename: Rosemary
authors.initials: R
authors.lastname: Gale
authors.forename: Raymond
authors.initials: R
authors.lastname: Camilleri
authors.forename: Ian
authors.initials: I
authors.lastname: Mackie
authors.forename: Samuel
authors.initials: S
authors.lastname: Machin
authors.forename: Paul
authors.initials: P
authors.lastname: Harrison
mesh_terms: D001772:Blood Cell Count; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000378:metabolism*; D005434:Flow Cytometry / Q000379:methods; D015200:Fluoroimmunoassay / Q000379:methods; D006801:Humans; D008833:Microcirculation; D018613:Microscopy, Confocal; D018621:PrPC Proteins; D012333:RNA, Messenger / Q000378:metabolism; D014471:Umbilical Veins
chemical_list: D018621:PrPC Proteins; D012333:RNA, Messenger