Prion Transport to Secondary Lymphoreticular System Tissues
Abstract
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 two animal models will be used. Genetically engineered mice that lack components of the complement system will be used to test the hypothesis that complement binding to PrPSc is involved in targeting of prions to cells in the spleen and uptake by macrophages. A second system will examine 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. The mouse and hamster systems investigate prion interactions with complement components based on differences of host and strain properties, respectively. This study will provide details into the host factors(s) involved in transport of prions to cells in the LRS, such as spleen.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jun 01, 2004
- Accession Number
- ADA430336
Entities
People
- Jason C. Bartz
Organizations
- Creighton University