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Cellular prion protein is expressed on endothelial cells and is released during apoptosis on membrane microparticles found in human plasma
Author(s) -
Šimák Jan,
Holada Karel,
D'Agnillo Felice,
Janota Jan,
Vostal Jaroslav G.
Publication year - 2002
Publication title -
transfusion
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.045
H-Index - 132
eISSN - 1537-2995
pISSN - 0041-1132
DOI - 10.1046/j.1537-2995.2002.00072.x
Subject(s) - flow cytometry , umbilical vein , apoptosis , microbiology and biotechnology , endothelial stem cell , biology , infectivity , cell , cell culture , chemistry , virology , in vitro , biochemistry , virus , genetics
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. STUDY DESIGN AND 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. CONCLUSION: 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.