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The expression of prion protein (PrP(C)) in the megakaryocyte lineage

R Starke1, P Harrison, I Mackie

  • 1Department of Haematology, University College London, London, UK. r.starke@ucl.ac.uk

Journal of Thrombosis and Haemostasis : JTH
|June 11, 2005
PubMed
Abstract

Insights

Cellular prion protein (PrP(C)) expression increases during megakaryocyte development. Found in platelet alpha-granules, PrP(C) in precursors may impact blood product safety and donor selection for variant Creutzfeldt-Jacob disease (vCJD).

Area of Science:

  • Hematology
  • Neuroscience
  • Biochemistry

Background:

  • Cellular prion protein (PrP(C)) is a normal protein that can misfold into disease-associated scrapie prion protein (PrP(Sc)).
  • Concerns exist regarding the transmission of PrP(Sc) via blood transfusions, particularly for variant Creutzfeldt-Jacob disease (vCJD).
  • PrP(C) is present in human blood, predominantly associated with platelets (84%), but its precursor source and quantity in platelets are not fully understood.

Purpose of the Study:

  • To investigate the expression of cellular prion protein (PrP(C)) within the megakaryocyte lineage.
  • To determine the cellular localization and potential source of PrP(C) in platelets.

Main Methods:

  • Studied PrP(C) expression in CD34+ cells, cultured megakaryocytes, and platelets.
  • Utilized electron microscopy, flow cytometry, semi-quantitative RT-PCR, and immunofluorescence confocal microscopy.

Main Results:

  • PrP(C) expression demonstrated an increase with megakaryocyte differentiation and polyploidization.
  • PrP(C) was localized within platelet alpha-granules.
  • The likely source of platelet PrP(C) is megakaryocyte precursors.

Conclusions:

  • PrP(C) expression is developmentally regulated within the megakaryocyte lineage.
  • The presence of PrP(C) in platelet alpha-granules suggests a megakaryocyte origin.
  • Findings have implications for blood donor selection and the preparation of cell-depleted blood products, especially concerning potential PrP(Sc) distribution.

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