title: Distribution and accumulation of PrP in gut-associated and peripheral lymphoid tissue of scrapie-affected Suffolk sheep.
abstract: The distribution of disease-associated prion protein (PrP) was investigated in eight animals (20-24 months of age) from a flock of Suffolk sheep that had experienced frequent cases of natural scrapie over a period of several years. Tissue from the central nervous system (CNS), alimentary tract, peripheral nervous system and lymphoreticular system was examined by histopathology and immunohistochemistry. The lymphoid tissues were subjected further to histoblot and immunofluorescence examination. The four clinically affected PrP(ARQ/ARQ) sheep had widespread accumulations of disease-associated PrP in the CNS, lymphoreticular system and peripheral ganglia. In the two PrP(ARQ/ARQ) sheep that did not show clinical signs of scrapie, only limited vacuolation and PrP accumulation were detected in the brain, but the results from the lymphoreticular system and peripheral nervous system were comparable with the clinically affected animals. The remaining PrP(ARR/ARR) and PrP(ARR/ARQ) sheep did not show proteinase K-resistant PrP accumulations in the lymphoid tissues examined and immunohistochemistry did not reveal the presence of disease-associated PrP. In lymphoid tissues of the PrP(ARQ/ARQ) sheep, the dominant localization of disease-associated PrP was in lymphoid nodules and double immunofluorescence labelling for PrP and CD21 provided further support for the role of follicular dendritic cells in scrapie in sheep. A striking finding in the present study was the large accumulations of disease-associated PrP in the lymphoid nodules of the alimentary tract at the late sub-clinical and clinical stage of the infection. The study also identified disease-associated PrP in extra-nodular sites of lymphoid tissues, such as the marginal zone of the spleen, and these observations were used to argue that cells of the mononuclear phagocyte system of sheep may be involved in the uptake, transport, elimination and shedding of the scrapie agent.
authors.affiliation: Department of Morphology, Genetics and Aquatic Biology, Norwegian School of Veterinary Science, PO Box 8146 Dep., N-0033 Oslo, Norway1.
authors.forename: Ragna
authors.initials: R
authors.lastname: Heggebø
authors.affiliation: Department of Morphology, Genetics and Aquatic Biology, Norwegian School of Veterinary Science, PO Box 8146 Dep., N-0033 Oslo, Norway1.
authors.forename: Charles McL
authors.initials: CM
authors.lastname: Press
authors.affiliation: Department of Morphology, Genetics and Aquatic Biology, Norwegian School of Veterinary Science, PO Box 8146 Dep., N-0033 Oslo, Norway1.
authors.forename: Gjermund
authors.initials: G
authors.lastname: Gunnes
authors.affiliation: Lasswade Veterinary Laboratory, Pentlands Science Park, Bush Loan, Penicuik, Midlothian EH26 0PZ, UK2.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: González
authors.affiliation: Lasswade Veterinary Laboratory, Pentlands Science Park, Bush Loan, Penicuik, Midlothian EH26 0PZ, UK2.
authors.forename: Martin
authors.initials: M
authors.lastname: Jeffrey
mesh_terms: D000818:Animals; D002490:Central Nervous System / Q000378:metabolism* / Q000473:pathology; D004064:Digestive System / Q000378:metabolism* / Q000473:pathology; D005455:Fluorescent Antibody Technique; D006651:Histocytochemistry; D008221:Lymphoid Tissue / Q000378:metabolism* / Q000473:pathology; D011328:Prions / Q000378:metabolism*; D012608:Scrapie / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D012756:Sheep
chemical_list: D011328:Prions