title: Human plasma thrombopoietin levels are regulated by binding to platelet thrombopoietin receptors in vivo.
abstract: BACKGROUND
  Data from several studies support the hypothesis that thrombopoietin (TPO) plasma levels are regulated via circulating platelet (PLT) numbers by binding to PLT TPO receptors (TPO-Rs). In this study, PLT numbers and TPO plasma levels were measured following the transfusion of unmanipulated, sham-saturated, and TPO-R-saturated PLT preparations to provide additional in vivo evidence for this regulatory mechanism.
  
  
  METHODS
  Following in vitro experiments to characterize pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF) binding characteristics, PLT numbers and TPO plasma levels were measured following the transfusion of unmanipulated, sham-saturated, and TPO-R-saturated PLT preparations in thrombocytopenic patients. Sham-saturated and TPO-R-saturated PLTs were prepared by a 1-hour incubation without and with 40 ng per mL of PEG-rHuMGDF, respectively, and subsequent washing and resuspension.
  
  
  RESULTS
  In vitro, 2.72 +/- 0.8 ng of PEG-rHuMGDF per 1 x 10(8) PLTs was bound within 1 hour of incubation. No additional PEG-rHuMGDF was bound following a second incubation with PEG-rHuMGDF, and bound PEG-rHuMGDF was not released over time. In vivo, TPO plasma levels decreased significantly (p < 0.001), by 30.7 +/- 5.8 and 20.9 +/- 2.1 percent after transfusion of unmanipulated and sham-saturated PLT preparations, respectively. However, TPO plasma levels were unaffected after the transfusion of TPO-R-saturated PLTs despite comparable transfusion-induced PLT count increases.
  
  
  CONCLUSIONS
  These data strongly support the concept that binding to PLT TPO-R is directly involved in human TPO plasma level regulation in vivo.
authors.affiliation: Department of Internal Medicine, University of Tübingen, Germany. stefan.scheding@charite.de
authors.forename: Stefan
authors.initials: S
authors.lastname: Scheding
authors.forename: Markus
authors.initials: M
authors.lastname: Bergmann
authors.forename: Akihiro
authors.initials: A
authors.lastname: Shimosaka
authors.forename: Philipp
authors.initials: P
authors.lastname: Wolff
authors.forename: Christoph
authors.initials: C
authors.lastname: Driessen
authors.forename: Gisa
authors.initials: G
authors.lastname: Rathke
authors.forename: Karl
authors.initials: K
authors.lastname: Jaschonek
authors.forename: Wolfram
authors.initials: W
authors.lastname: Brugger
authors.forename: Lothar
authors.initials: L
authors.lastname: Kanz
mesh_terms: D001792:Blood Platelets / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D009363:Neoplasm Proteins; D010976:Platelet Count; D017713:Platelet Transfusion; D011092:Polyethylene Glycols / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D018121:Receptors, Cytokine; D053628:Receptors, Thrombopoietin; D011994:Recombinant Proteins / Q000378:metabolism; D013921:Thrombocytopenia / Q000628:therapy; D013926:Thrombopoietin / Q000097:blood* / Q000378:metabolism
chemical_list: D009363:Neoplasm Proteins; D011518:Proto-Oncogene Proteins; D018121:Receptors, Cytokine; D053628:Receptors, Thrombopoietin; D011994:Recombinant Proteins; C103117:polyethylene glycol-recombinant human megakaryocyte growth and development factor; C082218:MPL protein, human; D011092:Polyethylene Glycols; D013926:Thrombopoietin