The expression of prion protein (PrP^C) in the megakaryocyte lineage

Background: Cellular prion protein (PrP^C) is a naturally occurring protein in normal individuals which adopts an abnormal conformation, termed scrapie prion protein (PrP^Sc) that is associated with disease. There is great concern that clinically asymptomatic variant Creutzfeldt-Jacob disease (vCJD) may transmit PrP^Sc in blood transfusion products. PrP^C is widely expressed and has been found in human blood. The majority of cellular borne PrP^C is associated with platelets (84%). Although PrP^C mRNA has been demonstrated in platelets, the quantity is unknown and may not reflect the total PrP^C present. Objective: To investigate the expression of PrP^C in the megakaryocyte lineage. Methods: The expression of PrP^C was studied in CD34⁺ cells, cultured megakaryocytes and platelets using electron microscopy, flow cytometry, semi-quantitative RT-PCR and immunofluorescence confocal microscopy. Results and conclusions: The expression of PrP^C appeared to increase with differentiation and polyploidization in the megakaryocyte lineage. PrP ^C was located within platelet α-granules and its source is likely to be from megakaryocyte precursors. If PrP^Sc has a similar distribution, these results have implications for the selection of blood donors and preparation of cell-depleted blood products.