NR ATNZ
AU Holada,K.; Simak,J.; Brown,P.W.; Vostal,J.G.
TI Differences in Expression of Cellular Prion Protein (PrPc) on Blood Cells of Non-human Primate Species
QU International Conference - Prion 2005: Between fundamentals and society's needs - 19.10.-21.10.2005, Congress Center Düsseldorf - Poster Session: Human prions, risk of blood products, and therapy HUMAN-23
PT Konferenz-Poster
AB
Two recent cases of probable vCJD transmission by transfusion emphasize the necessity of detailed understanding of blood related TSE pathogenesis. Non-humane primates are considered as more relevant models of human prion diseases than rodents. We have used quantitative flow cytometry with monoclonal antibodies FH11, 1562 and 6H4 against different parts of PrPc molecule for evaluation of PrPc expression on red blood cells, platelets and leukocytes of human (Homo sapiens), chimpanzee (Pan troglodytes), cynomolgus macaque (Macaca fascicularis), rhesus macaque (Macaca mulatta), common squirrel monkey (Saimiri sciureus) and lesser mouse lemur (Microcebus murinus). Remarkable differences between humans and non-human primates have been found in overall quantity and cell specificity of PrPc expression. Chimpanzee, rhesus macaque and squirrel monkey displayed much higher quantity of total blood cell membrane PrPc then human, due to markedly higher expression of PrPc on their red blood cells. Cynomolgus macaque and mouse lemur at the other hand demonstrated substantially lower levels of total blood cell membrane PrPc due to the lack of significant PrPc expression on red blood cells and platelets. All species displayed PrPc on leukocytes with highest levels on human cells. In contrast, only human, chimpanzee and to lower degree rhesus macaque expressed PrPc on platelets. Striking differences were demonstrated in the expression of PrPc on red blood cells between closely related primates. Chimpanzee red blood cells expressed more than 10 times more PrPc than their human counterparts. Even bigger difference was demonstrated between cynomolgus and rhesus macaques. If PrPc contributes to the propagation or transport of prion infectivity in blood, the species differences reported here need to be considered when extrapolating results of transmission studies with blood and blood components to humans.
*The authors' opinions do not represent the opinion of the US FDA. (GACR 310/04/0419)
IN Die Autoren stellten fest, dass es auch unter sehr nahe verwandten Primaten wie z.B. Schimpanse und Mensch oder verschiedenen Makakenarten enorme Unterschiede hinsichtlich der Expression des normalen zellulären Prionproteins auf roten und weißen Blutkörperchen sowie auf den Blutplättchen gibt. Diese Ergebnisse machen die Brauchbarkeit von Affenmodellen für die Untersuchung menschlicher TSE-Risiken äußerst fragwürdig.
AD Karel Holada, Institute of Immunology and Microbiology, 1st Faculty of Medicine, Charles University, Prague, Czech Republic; Karel Holada, Jan Simak, Jaroslav G. Vostal, Division of Hematology, CBER, FDA, Bethesda, USA; Paul Brown, 7815 Exeter Road, Bethesda, MD 20814, USA
SP englisch
PO Deutschland