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

Background: Cellular prion protein (Pi-PC) 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 PrPSc in blood transfusion products. PI-PC is widely expressed and has been found in human blood. The majority of cellular borne PrPC is associated with platelets (84%). Although PrPC rnRNA has been demonstrated in platelets, the quantity is unknown and may not reflect the total PrPC present. Objective: To investigate the expression of PrPC in the megakaryocyte lineage. Methods: The expression of PrPC was studied in CD34(+) cells, cultured nnegakaryocytes and platelets using electron microscopy; flow cytometry, semiquantitative RT-PCR and immunofluorescence confocal microscopy. Results and conclusions: The expression of PrPC appeared to increase with differentiation and polyploidization in the megakaryocyte lineage. PrPC was located within platelet a-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