NR ARLK
AU Heikenwalder,M.; Zeller,N.; Seeger,H.; Prinz,M.; Klöhn,P.C.; Schwarz,P.; Ruddle,N.H.; Weissmann,C.; Aguzzi,A.
TI Chronic lymphocytic inflammation specifies the organ tropism of prions
QU Science 2005 Feb 18; 307(5712): 1107-10
PT journal article
AB Prions typically accumulate in nervous and lymphoid tissues. Because proinflammatory cytokines and immune cells are required for lymphoid prion replication, we tested whether inflammatory conditions affect prion pathogenesis. We administered prions to mice with five inflammatory diseases of the kidney, pancreas, or liver. In all cases, chronic lymphocytic inflammation enabled prion accumulation in otherwise prion-free organs. Inflammatory foci consistently correlated with lymphotoxin up-regulation and ectopic induction of FDC-M1+ cells expressing the normal cellular prion protein PrPc. By contrast, inflamed organs of mice lacking lymphotoxin-alpha or its receptor did not accumulate the abnormal isoform PrPsc, nor did they display infectivity upon prion inoculation. By expanding the tissue distribution of prions, chronic inflammatory conditions may act as modifiers of natural and iatrogenic prion transmission.
IN Die Autoren inokulierten Hausmäuse, die an entzündlichen Erkrankungen von Niere, Pankreas oder Leber litten. Sie fanden PrPsc in diesen Organen nur dann, wenn sie entzündet waren. Dies geschah nicht bei Hausmäusen, die entweder Lymphotoxin alpha oder dessen Rezeptor nicht exprimieren können.
MH Animals; Chemokines, CC/metabolism; Hepatitis/immunology/metabolism/pathology; Inflammation/immunology/*metabolism/pathology; Islets of Langerhans/immunology/metabolism; Kidney/immunology/*metabolism/pathology; Liver/immunology/*metabolism/pathology; Lymphocytes/*immunology; Lymphotoxin/metabolism; Membrane Proteins/metabolism; Mice; Mice, Inbred C57BL; Mice, Transgenic; Nephritis/immunology/metabolism/pathology; Pancreas/immunology/*metabolism/pathology; Pancreatitis/immunology/metabolism/pathology; PrPc Proteins/metabolism; PrPsc Proteins/analysis/*metabolism; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.; Scrapie/immunology/*metabolism/pathology; Spleen/immunology/metabolism; Tissue Distribution
AD Institute of Neuropathology, University Hospital of Zürich, CH-8091 Zürich, Switzerland.
SP englisch
PO USA