Occurrence and cellular localization of PrP^d in kidneys of scrapie‐affected sheep in the absence of inflammation

Abstract

Following a preliminary description of disease‐associated prion protein (PrPd) deposition in the kidneys of scrapie‐affected sheep, detailed studies have been undertaken in order to evaluate the factors that could account for such PrPd accumulation and to determine the precise location of PrPd in the renal papillae. Immunohistochemical (IHC) examinations for PrPd were conducted in kidneys collected at post‐mortem from 30 naturally and 37 experimentally infected sheep. In addition, PrPd detection by western blot analysis (WB) and ultrastructural examination was carried out in a selection of kidneys. PrPd‐specific, multifocal IHC labelling with antibody R145 was achieved in the kidneys of 44% and 51% of the naturally and experimentally infected sheep, respectively. The specificity of these results was confirmed by further IHC and WB using several PrP antibodies raised to different amino acid sequences, and by examination of control tissues. PrPd was shown to accumulate in the interstitium of the renal papillae, in association with the cell membrane and lysosomes of fibroblast‐like cells, or extracellularly, in close contact with collagen and basal membranes. These deposits were unrelated to inflammatory changes in the kidney as shown by routine histology and by IHC for different immune cell markers. PrPd accumulated in the kidney of sheep that showed widespread PrPd deposition in the lymphoreticular system and had long incubation periods; these findings argue for a haematogenous origin of renal PrPd, although the precise site and mechanism–glomerular filtration and reabsorption at Henle's loop, or extravasation from vasa recta capillaries, or both–by which PrPd leaves the blood to accumulate in the interstitium of renal papillae remain to be determined. Either of these pathogenetic mechanisms could lead to environmental contamination via urine. Crown copyright © 2008. Reproduced with the permission of Her Majesty's Stationery Office. Published by John Wiley & Sons, Ltd.

Distribution of Peripheral PrPSc in Sheep with Naturally Acquired Scrapie

“…These mice deposit PrP Sc in their hearts (primarily between myocytes and around capillaries), renal glomerulus, gut, and islets of Langerhans after scrapie infection, and their blood contained high levels of scrapie infectivity [31], [32]. In our kidney samples, the majority of PrP Sc immunolabeling was observed in the renal papillae in accordance with previous studies [7]. However, in one case, granular immunolabeling at a renal corpuscle was observed.…”

“…With one exception (No. 4), PrP Sc immunolabeling was consistently found in the renal papillae interstice, as previously described [7]. In sheep No.…”

“…In naturally acquired scrapie, evidence suggests that the main route of entry of the agent is through the gut-associated lymphoid tissues, which then spreads to the CNS by centripetal transport along the peripheral nervous system (PNS; [3], [4]). However, the scrapie agent may also propagate to other organs; PrP Sc deposits in natural scrapie infections have been detected in placenta [5], skeletal muscle [6], kidney [7], [8], skin [9] and liver [10]. In addition, PrP Sc has also been associated with inflammation foci in different organs such as the lung and mammary glands from scrapie infected sheep [11], [12], [13].…”

Biochemical and immunohistochemical characterization of feline spongiform encephalopathy in a German captive cheetah

“…However, as shown by others (Ryder et al, 2001;Lezmi et al, 2003), the staining reaction seen in the glomeruli with different antibodies by IHC was interpreted as artificial, being similar to a labelling described by others for renal tubules. A reaction pattern involving epithelial cells or the interstitium of the renal papillae was not detectable (Ligios et al, 2007;Siso et al, 2008). Therefore, it remains unresolved which structures in the kidney contain the infectivity.…”

Detection of Chronic Wasting Disease Prions in Salivary, Urinary, and Intestinal Tissues of Deer: Potential Mechanisms of Prion Shedding and Transmission

“…However, researchers have reported the presence of PrP RES by immunohistochemistry (IHC), paraffin-embedded tissue (PET) blotting, or Western blotting (WB) in the kidneys of scrapie-affected sheep (28,35,46,47) and CWD ϩ deer (19), the lingual tissues of hamsters inoculated with the HY (hyper) strain of transmissible mink encephalopathy (10,34), and the salivary glands of scrapieaffected sheep (55) and CWD-infected cervidized transgenic mice (43). While the identification of protease-resistant prion proteins in cervid excretory tissues using conventional assays has proven difficult (2,13,14,24,49), bioassay studies identifying genuine prion infectivity in excretory tissues, albeit limited, date to the 1960s (16) and implicate both the salivary glands of Creutzfeldt-Jakob disease (CJD)-infected mice (41) and kidneys of scrapie-infected mice (12).…”