NR AUBS
AU Jeffrey,M.J.; Gonzalez,L.; Espenes,A.; Press,C.McL.; Martin,S.; Chaplin,M.J.; Davis,L.; Landsverk,T.; MacAldowie,C.; Eaton,S.; McGovern,G.
TI Transportation of prion protein across the intestinal mucosa of scrapie-susceptible and scrapie-resistant sheep
QU Journal of Pathology 2006 May; 209(1): 4-14
KI Journal of Pathology 2006 May; 209(1): 1-3. PMID: 16575798
PT journal article
AB To determine the mechanisms of intestinal transport of infection, and early pathogenesis, of sheep scrapie, isolated gut-loops were inoculated to ensure that significant concentrations of scrapie agent would come into direct contact with the relevant ileal structures (epithelial, lymphoreticular, and nervous). Gut loops were inoculated with a scrapie brain pool homogenate or normal brain or sucrose solution. After surgery, animals were necropsied at time points ranging from 15 min to 1 month and at clinical end point. Inoculum-associated prion protein (PrP) was detected by immunohistochemistry in villous lacteals and in sub-mucosal lymphatics from 15 min to 3.5 h post-challenge. It was also detected in association with dendritic-like cells in the draining lymph nodes at up to 24 h post-challenge. Replication of infection, as demonstrated by the accumulation of disease-associated forms of PrP in Peyer's patches, was detected at 30 days and sheep developed clinical signs of scrapie at 18-22 months post-challenge. These results indicate discrepancies between the routes of transportation of PrP from the inoculum and sites of de novo-generated disease-associated PrP subsequent to scrapie agent replication. When samples of homogenized inoculum were incubated with alimentary tract fluids in vitro, only trace amounts of protease-resistant PrP could be detected by western blotting, suggesting that the majority of both normal and abnormal PrP within the inoculum is readily digested by alimentary fluids.
MH Animals; Blotting, Western; Digestion; Gastrointestinal Contents; Genetic Predisposition to Disease; Genotype; Ileum/microbiology; Intestinal Mucosa/metabolism/*microbiology; Lymphoid Tissue/microbiology; Peyer's Patches/microbiology; Prions/isolation & purification/pathogenicity/*pharmacokinetics; Research Support, Non-U.S. Gov't; Scrapie/genetics/*microbiology; Sheep; Tissue Extracts/metabolism
AD Martin J. Jeffrey (m.jeffrey@vla.maff.gov.uk), Lorenzo González, Stuart Martin, Gillian McGovern, VLA Lasswade Veterinary Laboratory, Pentlands Science Park, Bush Loan, Penicuik, Edinburgh EH26 OPZ, Scotland, UK
SP englisch
PO England