NR AXSO
AU McGovern,G.; Jeffrey,M.
TI Sheep Scrapie Results in Lesions and Functional Disturbance of Lymphoid Tissues
QU International Conference - Prion 2007 (26.-28.9.2007) Edinburgh International Conference Centre, Edinburgh, Scotland, UK - Book of Abstracts: Pathology and Pathogenesis P03.01
IA http://www.prion2007.com/pdf/Prion Book of Abstracts.pdf
PT Konferenz-Poster
AB
Background: Transmissible spongiform encephalopathies or prion diseases often result in accumulation of disease-associated PrP (PrPd) in the lymphoreticular system, specifically in association with follicular dendritic cells (FDCs) and tingible body macrophages (TBMs) of secondary follicles.
Aims: We studied the effects of sheep scrapie on the structure and function of lymphoid tissue in tonsils and lymph nodes by light and electron microscopy.
Methods: Tissues from twenty sheep from different genotypes, naturally infected and with clinical signs of scrapie, and four uninfected control animals were studied using immunohistochemical and immunogold techniques.
Results: FDCs of sheep were grouped according to morphology as immature, mature and regressing. Scrapie was associated with FDC dendrite hypertrophy and electron dense deposit or vesicles. PrPd was located at the plasmalemma of both FDC dendrites and, infrequently, mature B cells. Abnormal electron dense deposits surrounding FDC dendrites were identified as immunoglobulins suggesting that excess immune complexes are retained and are indicative of an FDC dysfunction. Within scrapie-affected tissues, TBMs accumulated PrPd within endosomes and lysosomes. TBMs showed PrPd in association with the cell membrane, non-coated pits and vesicles, and also with discrete, large and random endoplasmic reticulum networks, which co-localised with ubiquitin.
Discussion: These observations suggest that PrPd is internalised via the caveolinmediated pathway, and causes an abnormal disease-related alteration in endoplasmic reticulum structure. In contrast to current dogma, this study shows that sheep scrapie is associated with cytopathology of germinal centres, which we attribute to abnormal antigen complex trapping by FDCs and abnormal endocytic events in TBMs. These sub-cellular alterations differ from those observed in scrapie-infected sheep brains, suggesting that different PrPd / cell membrane interactions occur in different cell types.
AD G. McGovern, M. Jeffrey, VLA (Lasswade), UK
SP englisch
PO Schottland
EA pdf-Datei und Poster (Postertitel: Scrapie-specific pathology of sheep lymphoid tissue)