Regulation of platelet lifespan in the presence and absence of thrombopoietin signaling

M. Lebois , M.R. Dowling, P. Gangatirkar, P. D. Hodgkin, B. T. Kile, W.S. Alexander, E. C. Josefsson

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Essentials We examined platelet survival in models of absent or enhanced thrombopoietin (TPO) signaling. Platelet lifespan is normal in transgenic mice with chronically enhanced TPO signaling. Mpl deficiency does not negatively affect platelet lifespan in the absence of thrombocytopenia. We conclude that TPO and its receptor Mpl are dispensable for platelet survival in adult mice. Summary: Background It is well established that thrombopoietin (TPO), acting via its receptor Mpl, is the major cytokine regulator of platelet biogenesis. The primary mechanism by which TPO signaling stimulates thrombopoiesis is via stimulation of Mpl-expressing hematopoietic progenitors; Mpl on megakaryocytes and platelets acts to control the amount of TPO available. TPO could potentially reduce platelet and/or megakaryocyte apoptosis, and therefore increase the platelet count. However, the effect of TPO receptor signaling on platelet survival is unresolved. Methods and results Here, we investigated platelet survival in mouse models of absent or enhanced TPO signaling. In the absence of thrombocytopenia, Mpl deficiency did not negatively influence platelet lifespan, and nor was platelet survival affected in transgenic mice with chronically increased TPO signaling. Conclusions We conclude that TPO and its receptor Mpl are dispensable for platelet survival in adult mice.

Original languageEnglish
Pages (from-to)1882-1887
Number of pages6
JournalJournal of Thrombosis and Haemostasis
Volume14
Issue number9
DOIs
Publication statusPublished - Sep 2016
Externally publishedYes

Keywords

  • animal models
  • apoptosis
  • Mpl protein, mouse
  • platelets
  • thrombopoietin

Cite this

Lebois , M., Dowling, M. R., Gangatirkar, P., Hodgkin, P. D., Kile, B. T., Alexander, W. S., & Josefsson, E. C. (2016). Regulation of platelet lifespan in the presence and absence of thrombopoietin signaling. Journal of Thrombosis and Haemostasis, 14(9), 1882-1887. https://doi.org/10.1111/jth.13397
Lebois , M. ; Dowling, M.R. ; Gangatirkar, P. ; Hodgkin, P. D. ; Kile, B. T. ; Alexander, W.S. ; Josefsson, E. C. / Regulation of platelet lifespan in the presence and absence of thrombopoietin signaling. In: Journal of Thrombosis and Haemostasis. 2016 ; Vol. 14, No. 9. pp. 1882-1887.
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abstract = "Essentials We examined platelet survival in models of absent or enhanced thrombopoietin (TPO) signaling. Platelet lifespan is normal in transgenic mice with chronically enhanced TPO signaling. Mpl deficiency does not negatively affect platelet lifespan in the absence of thrombocytopenia. We conclude that TPO and its receptor Mpl are dispensable for platelet survival in adult mice. Summary: Background It is well established that thrombopoietin (TPO), acting via its receptor Mpl, is the major cytokine regulator of platelet biogenesis. The primary mechanism by which TPO signaling stimulates thrombopoiesis is via stimulation of Mpl-expressing hematopoietic progenitors; Mpl on megakaryocytes and platelets acts to control the amount of TPO available. TPO could potentially reduce platelet and/or megakaryocyte apoptosis, and therefore increase the platelet count. However, the effect of TPO receptor signaling on platelet survival is unresolved. Methods and results Here, we investigated platelet survival in mouse models of absent or enhanced TPO signaling. In the absence of thrombocytopenia, Mpl deficiency did not negatively influence platelet lifespan, and nor was platelet survival affected in transgenic mice with chronically increased TPO signaling. Conclusions We conclude that TPO and its receptor Mpl are dispensable for platelet survival in adult mice.",
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Lebois , M, Dowling, MR, Gangatirkar, P, Hodgkin, PD, Kile, BT, Alexander, WS & Josefsson, EC 2016, 'Regulation of platelet lifespan in the presence and absence of thrombopoietin signaling' Journal of Thrombosis and Haemostasis, vol. 14, no. 9, pp. 1882-1887. https://doi.org/10.1111/jth.13397

Regulation of platelet lifespan in the presence and absence of thrombopoietin signaling. / Lebois , M.; Dowling, M.R.; Gangatirkar, P.; Hodgkin, P. D.; Kile, B. T. ; Alexander, W.S.; Josefsson, E. C.

In: Journal of Thrombosis and Haemostasis, Vol. 14, No. 9, 09.2016, p. 1882-1887.

Research output: Contribution to journalArticleResearchpeer-review

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AU - Lebois , M.

AU - Dowling, M.R.

AU - Gangatirkar, P.

AU - Hodgkin, P. D.

AU - Kile, B. T.

AU - Alexander, W.S.

AU - Josefsson, E. C.

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N2 - Essentials We examined platelet survival in models of absent or enhanced thrombopoietin (TPO) signaling. Platelet lifespan is normal in transgenic mice with chronically enhanced TPO signaling. Mpl deficiency does not negatively affect platelet lifespan in the absence of thrombocytopenia. We conclude that TPO and its receptor Mpl are dispensable for platelet survival in adult mice. Summary: Background It is well established that thrombopoietin (TPO), acting via its receptor Mpl, is the major cytokine regulator of platelet biogenesis. The primary mechanism by which TPO signaling stimulates thrombopoiesis is via stimulation of Mpl-expressing hematopoietic progenitors; Mpl on megakaryocytes and platelets acts to control the amount of TPO available. TPO could potentially reduce platelet and/or megakaryocyte apoptosis, and therefore increase the platelet count. However, the effect of TPO receptor signaling on platelet survival is unresolved. Methods and results Here, we investigated platelet survival in mouse models of absent or enhanced TPO signaling. In the absence of thrombocytopenia, Mpl deficiency did not negatively influence platelet lifespan, and nor was platelet survival affected in transgenic mice with chronically increased TPO signaling. Conclusions We conclude that TPO and its receptor Mpl are dispensable for platelet survival in adult mice.

AB - Essentials We examined platelet survival in models of absent or enhanced thrombopoietin (TPO) signaling. Platelet lifespan is normal in transgenic mice with chronically enhanced TPO signaling. Mpl deficiency does not negatively affect platelet lifespan in the absence of thrombocytopenia. We conclude that TPO and its receptor Mpl are dispensable for platelet survival in adult mice. Summary: Background It is well established that thrombopoietin (TPO), acting via its receptor Mpl, is the major cytokine regulator of platelet biogenesis. The primary mechanism by which TPO signaling stimulates thrombopoiesis is via stimulation of Mpl-expressing hematopoietic progenitors; Mpl on megakaryocytes and platelets acts to control the amount of TPO available. TPO could potentially reduce platelet and/or megakaryocyte apoptosis, and therefore increase the platelet count. However, the effect of TPO receptor signaling on platelet survival is unresolved. Methods and results Here, we investigated platelet survival in mouse models of absent or enhanced TPO signaling. In the absence of thrombocytopenia, Mpl deficiency did not negatively influence platelet lifespan, and nor was platelet survival affected in transgenic mice with chronically increased TPO signaling. Conclusions We conclude that TPO and its receptor Mpl are dispensable for platelet survival in adult mice.

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