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The expression of prion protein by endothelial cells: a source of the plasma form of prion protein?
Author(s) -
Starke Richard,
Drummond Olive,
MacGregor Ian,
Biggerstaff John,
Gale Rosemary,
Camilleri Raymond,
Mackie Ian,
Machin Samuel,
Harrison Paul
Publication year - 2002
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1046/j.1365-2141.2002.03847.x
Subject(s) - prion protein , protein expression , biology , chemistry , microbiology and biotechnology , medicine , biochemistry , pathology , gene , disease
Summary. 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 fluoroimmunoassay (DELFIA ® ) 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.