Divergent expression of cellular prion protein on blood cells of human and nonhuman primates.
BACKGROUND
Four recent transmissions of variant Creutzfeldt-Jakob disease infection by transfusion highlight the need for detailed understanding of blood-related prion pathogenesis. Nonhuman primates are the most relevant models of human prion diseases.


METHODS
Quantitative flow cytometry with monoclonal antibodies FH11, 3F4, and 6H4 against different parts of the normal cellular form of the prion protein (PrP(C)) was used to evaluate its expression on blood cells of humans, chimpanzees, cynomolgus macaques, rhesus macaques, squirrel monkeys, and microcebe lemurs.


RESULTS
Chimpanzees, rhesus macaques, and squirrel monkeys displayed a much higher quantity of total blood cell membrane PrP(C) than humans, due to a markedly higher expression of PrP(C) on their red blood cells (RBCs). In contrast, cynomolgus macaques and lemurs demonstrated substantially lower levels of membrane PrP(C) due to the lack of significant PrP(C) expression on RBCs and platelets (PLTs). All species displayed PrP(C) on white blood cells (WBCs), with the highest levels found on human cells. Only humans, chimpanzees, and to a lesser degree rhesus macaques expressed PrP(C) on PLTs.


CONCLUSIONS
If PrP(C) contributes to the propagation or transport of prion infectivity in blood, the differences reported here need to be considered when extrapolating results of transmission studies in primate models to blood and blood components in humans.
Holada
Karel
K
Department of Immunology and Microbiology, 1st Medical Faculty, Charles University, Prague, Czech Republic. Karel.Holada@LF1.cuni.cz
Simak
Jan
J
Brown
Paul
P
Vostal
Jaroslav G
JG
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D004912:Erythrocytes / Q000378:metabolism; D005434:Flow Cytometry; D006098:Granulocytes / Q000378:metabolism; D006801:Humans; D007900:Lemur / Q000097:blood; D007962:Leukocytes / Q000378:metabolism; D008214:Lymphocytes / Q000378:metabolism; D008251:Macaca / Q000097:blood; D009000:Monocytes / Q000378:metabolism; D002679:Pan troglodytes / Q000097:blood; D011323:Primates / Q000097:blood*; D011328:Prions / Q000032:analysis / Q000097:blood* / Q000276:immunology; D012453:Saimiri / Q000097:blood; D013045:Species Specificity
D000911:Antibodies, Monoclonal; D011328:Prions