Abstract
BackgroundIn classical scrapie, the disease-associated abnormal isoform (PrPSc) of normal prion protein accumulates principally in the nervous system and lymphoid tissues of small ruminants. Lymph nodes traffic leukocytes via lymphatic and blood vasculatures but hemal nodes lack lymphatic vessels and thus traffic leukocytes only via the blood. Although PrPSc accumulation profiles are well-characterized in ovine lymphoid tissues, there is limited information on such profiles in hemal nodes. Therefore, the objective of this study was to compare the follicular accumulation of PrPSc within hemal nodes and lymph nodes by prion epitope mapping and western blot studies.ResultsOur studies found that PrPSc accumulation in 82% of animals’ abdominal hemal nodes when PrPSc is detected in both mesenteric and retropharyngeal lymph nodes collected from preclinical and clinical, naturally and experimentally (blood transfusion) scrapie-infected sheep representing all three major scrapie-susceptible Prnp genotypes. Abdominal hemal nodes and retropharyngeal lymph nodes were then used to analyze immune cell phenotypes and PrPSc epitope mapping by immunohistochemistry and PrPSc banding patterns by western blot. Similar patterns of PrPSc accumulation were detected within the secondary follicles of hemal nodes and retropharyngeal lymph nodes, where cellular labeling was mostly associated with macrophages and follicular dendritic cells. The pattern of PrPSc accumulation within hemal nodes and retropharyngeal lymph nodes also did not differ with respect to epitope mapping with seven mAbs (N-terminus, n = 4; globular domain, n = 2; C-terminus, n = 1) in all three Prnp genotypes. Western blot analysis of hemal node and retropharyngeal lymph node homogenates revealed identical three banding patterns of proteinase K resistant PrPSc.ConclusionDespite the anatomical difference in leukocyte trafficking between lymph nodes and hemal nodes, the follicles of hemal nodes appear to process PrPSc similarly to lymph nodes.
Highlights
In classical scrapie, the disease-associated abnormal isoform (PrPSc) of normal prion protein accumulates principally in the nervous system and lymphoid tissues of small ruminants
PrPSc accumulates within the hemal nodes of scrapie-infected sheep Lambs became scrapie infected either through natural exposure or by intravenous transfusion of whole blood or blood cell fractions isolated from scrapie-infected sheep
PrPSc accumulation in the hemal nodes was detected in all three major scrapie susceptible Prnp genotypes in both scrapie-infected groups (Table 2)
Summary
The disease-associated abnormal isoform (PrPSc) of normal prion protein accumulates principally in the nervous system and lymphoid tissues of small ruminants. Detection of PrPSc in lymphoid tissues very early in the course of disease suggests that prions may disseminate within the body via the blood and lymphatic vascular systems before entering the central nervous system [3,10]. Hemal nodes lack both afferent and efferent lymphatic vessels and receive leukocytes only from the blood, and vascular sinuses are filled with blood rather than lymph [23]. Despite the lack of lymphatic vessels in the spleen, prions can be readily detected in the spleen as early as three months of age in lambs born to scrapie-infected dams [3,10]. Since prions are present within the different blood components and hemal nodes structurally and functionally resemble spleen, it seems likely that the cellular components of hemal nodes are exposed to prions and might accumulate PrPSc and participate as a site of prion replication
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