Similar turnover and shedding of the cellular prion protein in primary lymphoid and neuronal cells

The cellular prion protein (PrPc) is essential for pathogenesis and transmi ssion of prion diseases. Although prion replication in the brain is accompa nied by neurodegeneration, prions multiply efficiently in the lymphoreticul ar system without any detectable pathology. We have used pulse-chase metabo lic radiolabeling experiments to investigate the turnover and processing of PrPc in primary cell cultures derived from lymphoid and nervous tissues. S imilar kinetics of PrPc degradation were observed in these tissues. This in dicates that the differences between these two organs with respect to their capacity to replicate prions is not due to differences in the turnover of PrPc. Substantial amounts of a soluble form of PrP that lacks the glycolipi d anchor appeared in the medium of splenocytes and cerebellar granule cells . Soluble PrP was detected in murine and human serum, suggesting that it mi ght be of physiological relevance.