The expression of prion protein by endothelial cells: a source of the plasma form of prion protein?

The neuronal prion protein (PrP(C)) is also expressed within peripheral tissues including human blood. The majority of blood PrP(C) is found within the plasma fraction. We hypothesized that the vascular endothelium could be a source of this PrP(C). Reverse transcription polymerase chain reaction demonstrated that both human umbilical vein endothelial cells (HUVEC) and human microvascular endothelial cells (HMEC-1) expressed PrP(C) mRNA. Flow cytometry confirmed PrP(C) expression on HMEC-1s and HUVECs (120 900 +/- 15 058 and 58 327 +/- 4577 molecules PrP(C)/cell respectively), with no upregulation following cellular activation. Confocal immunofluorescence microscopy confirmed that HMEC-1s and HUVECs were positive for PrP(C) on the plasma membrane. Time-resolved dissociation-enhanced (DELFIA(R)) analysis of cell culture medium demonstrated a slow constitutive release of soluble PrP(C) not associated with activation. In contrast to von Willebrand factor antigen, PrP(C) plasma levels in vivo decrease following desmopressin therapy in patients with von Willebrand disease. Measurement of PrP(C) plasma levels in patients with varying blood counts demonstrated no association between cell count and PrP(C) concentration. However, there was a higher level of PrP(C) in plasma from patients with end-stage renal failure. In conclusion, endothelial cells of both macrovascular and microvascular origin expressed high levels of PrP(C) which can be constitutively released into the cell culture medium.