Bovine macrophage degradation of scrapie and BSE PrPSc.

Abstract

Transmissible spongiform encephalopathies (TSEs), such as bovine spongiform encephalopathy (BSE) and scrapie, display long incubation periods before PrP(Sc) accumulates in the central neuronal system (CNS). The precise role that phagocytic cells, such as macrophages, play in prion pathogenesis is uncertain. In this study, the involvement of bovine macrophages at the early stage of prion infection was studied. Brain homogenates of mouse scrapie and BSE were degraded sequentially in the bovine macrophage cell line, Bo120, and freshly prepared in monocyte-derived macrophages from peripheral blood. Mouse scrapie brain homogenates degraded in Bo120 cells were inoculated intraperitoneally to C57BL mice, showing that the degree of cellular degradation (2h, 10, 28, and 36d) correlated with survival periods (288, 303, 324, and 340d, respectively). Partial colocalizations of PrP and lysosomes were observed in Bo120 cells by confocal microscopy. These results suggest that bovine macrophages have the ability to take up and degrade PrP(Sc), resulting in decreased TSE infectivity in mice.