The Post-Transfusion Recovery and Survival of Red Blood Cells in Mice Is Affected by the Expression of Cellular Prion Protein

• Published in: Blood 2006-11, Vol.108 (11), p.959-959
• Main Authors: Holada, Karel, Simak, Jan, Vostal, Jaroslav G.
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V108.11.959.959

Three documented transfusion cases of vCJD underline the need of better insight in blood prion protein biology. Cellular prion protein (PrPc) plays key role in the pathophysiology of prion diseases. Its expression by cells is necessary for amplification of infectious prions and the disease process itself. Physiological function of PrPc remains obscure. Its clarification may provide important clues for the development of urgently needed blood test and effective disease treatment. PrPc is expressed on CD34+ hematopoietic stem cells and its expression is regulated during blood cell differentiation. Recently the importance of PrPc for self-renewal of long-term repopulating hematopoietic stem cells was suggested and other studies reported the protective function of PrPc against oxidative stress and apoptosis in various cell cultures. We previously demonstrated that human as well as mouse red blood cells (RBC) express approximately 200 PrPc molecules / cell (Holada et al., BJH 2000, 110, 472–80). To test if the PrPc expression plays a role in the post-transfusion recovery and survival of RBC we carried out transfusion study in mice. RBC isolated from blood of wild type (WT) and PrP knockout (KO) FVB mice were labeled “in vitro” by different levels of NHS-biotin. The labeling was optimized to allow simultaneous detection of both populations of RBC in mouse blood using flow cytometry. To exclude the influence of different level of cell biotinylation on the experiment outcome two mixtures of RBC were prepared. The first contained KO RBC labeled with high and WT RBC with low level of biotin and the second mixture contained cells labeled “vice versa”. Each mixture was injected via tail vein in a group of WT mice (n=5) and the survival of RBCs was followed. Samples were analyzed on day 1, 2, 3, 6, 9, 15, 21 and 29. The count of biotinylated RBC was measured in comparison to 100 000 nonlabeled recipient RBC. Simultaneously the expression of PrPc on RBC was monitored using flow cytometry with MAb 6H4. KO RBC displayed significantly higher first day post-transfusion recovery compared to WT RBC in both groups of mice (81 ± 3 % vs. 74 ± 3 %, P