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Human plasma thrombopoietin levels are regulated by binding to platelet thrombopoietin receptors in vivo

Scheding, Stefan LU ; Bergmann, Markus; Shimosaka, Akihiro; Wolff, Philipp; Driessen, Christoph; Rathke, Gisa; Jaschonek, Karl; Brugger, Wolfram and Kanz, Lothar (2002) In Transfusion 42(3). p.321-327
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. STUDY DESIGN AND 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... (More)
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. STUDY DESIGN AND 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. CONCLUSION: These data strongly support the concept that binding to PLT TPO-R is directly involved in human TPO plasma level regulation in vivo. (Less)
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author
publishing date
type
Contribution to journal
publication status
published
subject
in
Transfusion
volume
42
issue
3
pages
321 - 327
publisher
Wiley-Blackwell
external identifiers
  • pmid:11961237
  • scopus:0036516690
ISSN
1537-2995
DOI
10.1046/j.1537-2995.2002.00047.x
language
English
LU publication?
no
id
6085f3e8-5e9b-4d0c-a3a1-91f03a02d0c0 (old id 1123819)
date added to LUP
2008-05-30 15:17:56
date last changed
2017-03-12 04:07:35
@article{6085f3e8-5e9b-4d0c-a3a1-91f03a02d0c0,
  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. STUDY DESIGN AND 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 &lt; 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. CONCLUSION: These data strongly support the concept that binding to PLT TPO-R is directly involved in human TPO plasma level regulation in vivo.},
  author       = {Scheding, Stefan and Bergmann, Markus and Shimosaka, Akihiro and Wolff, Philipp and Driessen, Christoph and Rathke, Gisa and Jaschonek, Karl and Brugger, Wolfram and Kanz, Lothar},
  issn         = {1537-2995},
  language     = {eng},
  number       = {3},
  pages        = {321--327},
  publisher    = {Wiley-Blackwell},
  series       = {Transfusion},
  title        = {Human plasma thrombopoietin levels are regulated by binding to platelet thrombopoietin receptors in vivo},
  url          = {http://dx.doi.org/10.1046/j.1537-2995.2002.00047.x},
  volume       = {42},
  year         = {2002},
}