The normal cellular prion protein is strongly expressed by myeloid dendritic cells

被引:68
作者
Burthem, J
Urban, B
Pain, A
Roberts, DJ [1 ]
机构
[1] John Radcliffe Hosp, Natl Blood Serv, Oxford Ctr, Oxford OX3 9DU, England
[2] Univ Oxford, Nuffield Dept Biochem & Cellular Sci, Oxford, England
[3] Univ Manchester, Dept Biomed Sci, Manchester M60 1QD, Lancs, England
关键词
D O I
10.1182/blood.V98.13.3733
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Abnormal isoforms of the prion protein (PrPSc) that cause prion diseases are propagated and spread within the body by "carrier" cell(s). Cells of the immune system have been strongly implicated in this process. In particular, PrPSc is known to accumulate on follicular dendritic cells (FDCs) in individuals affected by variant Creutzfeld-Jakob disease. However, FDCs do not migrate widely and the natural history of prion disorders suggests other cells may be required for the transport of PrPSc from the site of ingestion to lymphoid organs and the central nervous system. Substantial evidence suggests that the spread of PrPSc requires bone marrow-derived cells that express normal cellular prion protein (PrPC). This study examined the expression of PrPC on bone marrow-derived cells that interact with lymphoid follicles. High levels of PrPC are present on myeloid dendritic cells (DCs) that surround the splenic white pulp. These myeloid DCs are ontologically and functionally distinct from the FDCs. Consistent with these observations, expression of PrPC was strongly induced during the generation of mature myeloid DCs in vitro. in these cells PrPC colocalized with major histocompatibility complex class II molecules at the level of light microscopy. Furthermore, given the close anatomic and functional connection of myeloid DCs with lymphoid follicles, these results raise the possibility that myeloid DCs may play a role in the propagation of PrPSc in humans. (C) 2001 by The American Society of Hematology.
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页码:3733 / 3738
页数:6
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