title: Role of cell death in the propagation of PrP(Sc) in immune cells.
abstract: A number of studies have suggested that macrophages, dendritic cells, and follicular dendritic cells play an important role in the propagation of PrP(Sc). Both accumulation and proteolysis of PrP(Sc) have been demonstrated in peripheral macrophages. Macrophages may act as reservoirs for PrP(Sc) particles if the cells die during transient PrP(Sc) propagation. However, whether cell death plays a role in PrP(Sc) propagation in macrophages remains unclear. In this study, we investigated the possibility of propagation and transmission of PrP(Sc) between dead immune cells and living neural cells. We found that under specific conditions, transient PrP(Sc) propagation occurs in dead cells, indicating that interaction between PrP(C) and PrP(Sc) on plasma membrane lipid rafts might be important for PrP(Sc) propagation. Co-culturing of killed donor PrP(Sc)-infected macrophages with recipient N2a-3 neuroblastoma cells accelerated PrP(Sc) transmission. Our results suggest that cell death may play an important role in PrP(Sc) propagation, whereas transient PrP(Sc) propagation in macrophages has little effect on PrP(Sc) transmission.
authors.affiliation: Laboratory of Food and Environmental Hygiene, Veterinary Medicine, Faculty of Applied Biological Sciences, Gifu University, 1-1 Yanagido, Gifu, Japan.
authors.forename: Kenichi
authors.initials: K
authors.lastname: Takahashi
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Inoshima
authors.forename: Naotaka
authors.initials: N
authors.lastname: Ishiguro
mesh_terms: D016923:Cell Death; D002460:Cell Line; D003713:Dendritic Cells / Q000378:metabolism*; D006801:Humans; D008264:Macrophages / Q000378:metabolism*; D021962:Membrane Microdomains / Q000378:metabolism; D009474:Neurons / Q000378:metabolism / Q000502:physiology*; D018621:PrPC Proteins / Q000378:metabolism*; D018620:PrPSc Proteins / Q000378:metabolism*
chemical_list: D018621:PrPC Proteins; D018620:PrPSc Proteins