Cellular prion protein is expressed on peripheral blood mononuclear cells but not platelets of normal and scrapie-infected sheep

Background and Objectives. Transmissible spongiform encephalopathies (TSEs) including sheep scrapie are characterized by the conversion of a normal, cellular prion protein (PrPc) to an abnormal protease-resistant form (PrPSc). Like human peripheral blood, the peripheral blood of scrapie-infected sheep remains one possible source of disease transmission. As a first step in understanding the disease requirements in the natural scrapie host, the presence of PrPc was evaluated in peripheral blood cells from five normal and five scrapie-infected Suffolk sheep. Design and Methods. Live peripheral blood cells from normal and scrapie-infected sheep were analyzed for the presence of PrP using flow cytometry and reverse transcriptase-polymerase chain reaction (RT-PCR). Results. PrP mRNA was detected in peripheral blood mononuclear cells (PBMC) but not in platelets or granulocytes. Consistent with PrP mRNA expression, cell-surface expressed PrP was detected on PBMC, but was not detected on granulocytes, platelets, or erythrocytes. Two-color flow cytometric analysis of PBMC specific phenotypes revealed that regardless of scrapie-status, expression of PrP was significantly higher an B2 positive B-lymphocytes than on CD4, CD8, WC1 positive T-lymphocytes or CD14 positive monocytes, In addition, PrP expressed on PBMC from normal and scrapie-infected sheep was sensitive to proteinase K (PK) and phosphatidylinositol-specific phospholipase C (PIPLC) Interpretation and Conclusions. Regardless of the scrapie-status of the sheep, resting PBMC transcribe Pr-Pc and express Pr-Pc as a cell-surface protein sensitive to both PK and PIPLC. Because of the abundance of Pr-Pc on PBMC, future diagnostic tests using PK and PIPLC to discriminate between protease sensitive and resistant PrP must be carefully evaluated. (C) 2001, Ferrata Storti Foundation.