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Thromb Haemost 2000; 83(04): 610-616
DOI: 10.1055/s-0037-1613872
Commentary
Schattauer GmbH

Thrombopoietin Increases Platelet Sensitivity to α-Thrombin via Activation of the ERK2-cPLA2 Pathway

Gijsbert van Willigen
1   From the Department of Haematology, University Hospital Utrecht, and Institute for Biomembranes, University of Utrecht, the Netherlands
,
Gertie Gorter
1   From the Department of Haematology, University Hospital Utrecht, and Institute for Biomembranes, University of Utrecht, the Netherlands
,
Jan-Willem N. Akkerman
1   From the Department of Haematology, University Hospital Utrecht, and Institute for Biomembranes, University of Utrecht, the Netherlands
› Author AffiliationsThe authors like to thank Hans Bos and Barbara Franke for many discussions and crytically reading the manuscript, and Boudewijn Burgering, Yolanda Simarro-Doorten and Nico Maris for their help to set-up the ERK2 assay. This study was supported by a grant of the Netherlands Organization for Scientific Research/Netherlands Heart Foundation (grant 902-526-094/940-50-102). JWNA is supported the Netherlands Thrombosis Foundation. GvW is researchfellow of the Catharijne Foundation and supported by the Dirk Zwager-Assink Foundation.
Further Information

Publication History

Received 06 June 1999

Accepted after revision 09 December 1999

Publication Date:
08 December 2017 (online)

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Summary

Thrombopoietin (TPO) regulates stem cell proliferation and maturation of megakaryocytes by activating the c-Mpl-receptor, a member of the hematopoietic cytokine family. As human platelets possess c-Mplreceptors and supraphysiological concentrations of TPO trigger platelet aggregation and secretion, we searched for the signalling pathways through which the c-Mpl-receptor might activate platelets. A physiological concentration of TPO (20 ng/mL) did not trigger platelet functions, but increased their sensitivity to α-thrombin resulting in a 4-fold faster dense granule secretion. The effect of TPO was abolished by indomethacin and caused by synergism with signal generation by α-thrombin at the level of the cytosolic phospholipase A2 (cPLA2) pathway resulting in more arachidonate release, cPLA2 phosphorylation and thromboxane A2 formation. A similar synergism was seen at the level of extracellular signal-regulated kinase 2 (ERK2 or p42-MAPK). These data suggest, that TPO increases the sensitivity of platelets to α-thrombin by enhancing cPLA2 activation via the ERK2-cPLA2 pathway.

Keywords

Thrombopoietin - platelet sensitisation - cytosolic phospholipase A2 - thromboxane A2 - extracellular signal-regulated kinase
 

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