Platelets Release Thrombopoietin (Tpo) upon Activation: another Regulatory Loop in Thrombocytopoiesis?

Claudia C. Folman; Gabor E. Linthorst; Jan van Mourik; Gijsbert van Willigen; Evert de Jonge; Marcel Levi; Masja de Haas; Albert EGKr von dem Borne

doi:10.1055/s-0037-1613944

Thrombosis and Haemostasis, Inhaltsverzeichnis

Thromb Haemost 2000; 83(06): 923-930
DOI: 10.1055/s-0037-1613944

Commentary

Schattauer GmbH

Platelets Release Thrombopoietin (Tpo) upon Activation: another Regulatory Loop in Thrombocytopoiesis?

Claudia C. Folman

¹From the Division of Internal Medicine and Dept. of Haematology, Academic Medical Centre, Amsterdam, the Netherlands

²Dept. of Experimental Immunohaematology, CLB and the Laboratory of Experimental and Clinical Immunology, Academic Medical Centre, University of Amsterdam, Amsterdam

,

Gabor E. Linthorst

¹From the Division of Internal Medicine and Dept. of Haematology, Academic Medical Centre, Amsterdam, the Netherlands

,

Jan van Mourik

³Dept. of Blood Coagulation, CLB and the Laboratory of Experimental and Clinical Immunology, Academic Medical Centre, University of Amsterdam, Amsterdam

,

Gijsbert van Willigen^#

⁴Dept of Haematology, Thrombosis and Haemostasis Laboratory, University Medical Centre Utrecht, the Netherlands

,

Evert de Jonge

¹From the Division of Internal Medicine and Dept. of Haematology, Academic Medical Centre, Amsterdam, the Netherlands

,

Marcel Levi

¹From the Division of Internal Medicine and Dept. of Haematology, Academic Medical Centre, Amsterdam, the Netherlands

,

Masja de Haas

²Dept. of Experimental Immunohaematology, CLB and the Laboratory of Experimental and Clinical Immunology, Academic Medical Centre, University of Amsterdam, Amsterdam

,

Albert EGKr von dem Borne

¹From the Division of Internal Medicine and Dept. of Haematology, Academic Medical Centre, Amsterdam, the Netherlands

²Dept. of Experimental Immunohaematology, CLB and the Laboratory of Experimental and Clinical Immunology, Academic Medical Centre, University of Amsterdam, Amsterdam

› Institutsangaben

Abstract

Summary

Thrombopoietin is produced at a constant rate by the liver and kidney and is removed from the circulation upon binding and subsequent uptake via the Tpo receptor, c-Mpl, expressed by platelets and megakaryocytes. Apart from uptake, this study shows that platelets can also function as a storage pool for Tpo.

Upon stimulation with various platelet agonists, full-length biologically active Tpo was released by platelets. Platelet fractionation experiments indicated that this Tpo most likely is contained in the granules. When platelets were preincubated with Tpo-peptide mimetic or truncated Tpo prior to maximal activation, a three- to fivefold increment in Tpo release was seen, whereas, the release of other granule proteins such as vWF-propeptide or serotonin remained unchanged. Therefore, the Mpl agonists might compete with Mpl-bound Tpo, thereby releasing Tpo into the platelet supernatant.

Intravascular release of Tpo by platelets might occur in patients with massive platelet activation, as occurs in patients with disseminated intravascular coagulation. The Tpo concentration in these patients is elevated (p <0.01) and correlates with markers for thrombin generation, TAT complexes and Fl+2 (r_p =0.8 and 0.9; p <0.01). This suggests that the increment in Tpo concentration was attributed to Tpo release by activated platelets in vivo, which might be instrumental in subsequent stimulation of thrombocytopoiesis.

Keywords

Thrombopoietin - Tpo - platelets activation - c-Mpl

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Referenzen

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