Abstract
The cellular prion protein (PrPc) is a glycolipid-anchored cell surface protein that usually exhibits three glycosylation states. Its post-translationally modified isoform, PrPsc, is involved in the pathogenesis of various transmissible spongiform encephalopathies (TSEs). In bovine species, BSE infectivity appears to be restricted to the central nervous system; few or no detectable infectivity is found in lymphoid tissues in contrast to scrapie or variant CJD. Since expression of PrPc is a prerequisite for prion replication, we have investigated PrPc expression by bovine immune cells. Lymphocytes from blood and five different lymph organs were isolated from the same animal to assess intra- and interindividual variability of PrPc expression, considering six individuals. As shown by flow cytometry, this expression is absent or weak on granulocytes but is measurable on monocytes, B and T cells from blood and lymph organs. The activation of the bovine cells produces an upregulation of PrPc. The results of our in vitro study of PrPc biosynthesis are consistent with previous studies in other species. Interestingly, western blotting experiments showed only one form of the protein, the diglycosylated band. We propose that the glycosylation state could explain the lack of infectivity of the bovine immune cells.
Highlights
Transmissible spongiform encephalopathies (TSEs) are neurodegenerative diseases including bovine spongiform encephalopathy (BSE), scrapie, Creutzfeldt-Jakob disease (CJD) and variant, fatal familial insomnia, Gerstmann-Straussler-Scheinker’s syndrome and Kuru
Different cells of the immune system appear implicated in the pathogenesis: lymphocytes, Follicular dendritic cells (FDCs), macrophages and dendritic cells (Klein et al, 1997; Brandner et al, 1999; Brown et al, 1999; Montrasio et al, 2000; Beringue et al, 2000; Huang et al, 2002)
FDCs could act as key players, B lymphocytes and other immune cells having an indirect role as shown by the different studies using immunodeficient mice (Klein et al, 1998), or knock-out mice for the lymphotoxin or TNF pathways (Mabbott et al, 2000;2002; Prinz et al, 2002)
Summary
Transmissible spongiform encephalopathies (TSEs) are neurodegenerative diseases including bovine spongiform encephalopathy (BSE), scrapie, Creutzfeldt-Jakob disease (CJD) and variant (vCJD), fatal familial insomnia, Gerstmann-Straussler-Scheinker’s syndrome and Kuru. The cellular form of the prion protein (PrPc) is currently thought to be the substrate for the synthesis of its pathogenic counterpart (Bueler et al, 1993). In the central nervous system, PrPc expression is very high and correlates with an important accumulation of infectivity in the TSEs (Wells et al, 1994). FDCs could act as key players, B lymphocytes and other immune cells having an indirect role as shown by the different studies using immunodeficient mice (Klein et al, 1998), or knock-out mice for the lymphotoxin or TNF pathways (Mabbott et al, 2000;2002; Prinz et al, 2002)
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