期刊
TRANSFUSION
卷 50, 期 2, 页码 452-466出版社
WILEY
DOI: 10.1111/j.1537-2995.2009.02437.x
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类别
资金
- European Community [QLK1-CT-2002-01096]
- German Federal Ministry of Health
BACKGROUND: The cellular prion protein (PrPc) plays a central role in prion diseases such as variant Creutzfeldt-Jakob disease. This disease can be transmitted by blood transfusion. However, the exact kinetics of blood infectivity and the blood fraction carrying infectivity have not yet been identified. STUDY DESIGN AND METHODS: Simian PrPc epitopes were mapped by flow cytometry using monoclonal antibodies (MoAbs). A whole blood/no wash protocol was established, validated, and applied to investigate peripheral blood cell-associated PrPc expression profiles in bovine spongiform encephalopathy (BSE)-infected cynomolgus monkeys and age-/sex-matched controls. In addition, physiologic expression patterns on blood cells and in lymphoid tissues were determined. RESULTS: In BSE-infected macaques, blood lymphocyte-associated PrPc fluorescence gradually increased years before the onset of clinical signs (p(F) test < 0.0001). The increase in fluorescence intensity was detectable with MoAb 12F10, whereas we failed to detect an increase with 3F4. In parallel, plasma concentrations of soluble CD230 also increased. Centrifugation of lymphocytes almost completely eliminated differences between infected and noninfected animals, most likely caused by a partial loss in cell-associated CD230 into the plasma supernatant. CONCLUSION: Blood lymphocytes from asymptomatically infected as well as diseased macaques were characterized by increased CD230 fluorescence, and phosphatidylinositol-phospholipase C-resistant PrP molecules contributed at least partially to this increase. Conformational changes within PrPc molecules may be the underlying mechanism for the increased PrPc fluorescence. This cell-associated phenomenon contributed at least partially to an increase in soluble plasma-derived PrPc levels. It is not yet known whether these changes reflect infectivity.
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