Prion Transport to Secondary Lymphoreticular System Tissues
Annual rept. 1 Jun 2004-31 May 2005
CREIGHTON UNIV OMAHA NE
Pagination or Media Count:
The long-term objective of this proposal is to identify mechanisms of prion transport to secondary lymphoreticular system LRS tissues. The hypothesis to be tested is that following peripheral exposure to prions, host proteins e.g. complement bind prions allowing for trapping by cells in the spleen and enhancing uptake by macrophages, which are cells that are responsible for destruction of foreign proteins. To investigate this hypothesis we will examine the disease development of a prion strain DY TME that does not replicate in the spleen of hamsters. We will use this system to test the hypothesis that DY TME is not bound by complement resulting in its absence in the spleen. This study will provide details into the host factorss involved in transport of prions to cells in the LRS, such as spleen. We have shown differences in the migration of female protein, the hamster homologue of serum amyloid protein, in TME-infected hamsters. We can selectively immunoprecipitate PrPSc for experiments to determine if PrPSc is opsonized. We also have preliminary data suggesting differences in the susceptibility of HY and DY TME to phagocytosis and degradation by macrophages.
- Medicine and Medical Research