Human plasma thrombopoietin levels are regulated by binding to platelet thrombopoietin receptors in vivo
(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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1123819
- author
- Scheding, Stefan LU ; Bergmann, Markus ; Shimosaka, Akihiro ; Wolff, Philipp ; Driessen, Christoph ; Rathke, Gisa ; Jaschonek, Karl ; Brugger, Wolfram and Kanz, Lothar
- publishing date
- 2002
- 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
- additional info
- The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Hematology/Transplantation (013022014)
- id
- 6085f3e8-5e9b-4d0c-a3a1-91f03a02d0c0 (old id 1123819)
- date added to LUP
- 2016-04-01 16:10:42
- date last changed
- 2022-04-22 20:09:30
@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 < 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}}, doi = {{10.1046/j.1537-2995.2002.00047.x}}, volume = {{42}}, year = {{2002}}, }