Action of thrombopoietin at the megakaryocyte progenitor level is critical for the subsequent proplatelet production

K. Horie, H. Miyazaki, T. Hagiwara, E. Tahara, A. Matsumoto, T. Kadoya, K. Ogami, T. Kato

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34 Citations (Scopus)

Abstract

Formation of proplatelets from megakaryocytes is believed to be the first step of platelet production in vitro. In this study, we evaluated the effects of recombinant human thrombopoietin (hTPO) on the development of proplatelets from a GpIIb/IIIa+ population of rat bone marrow cells highly enriched for late megakaryocyte progenitors (GpIIb/IIIa+ CFU-MK) that we recently found to be a primary target population of TPO. Quantitative measurement of hTPO-induced proplatelet formation was performed in liquid cultures. Proplatelet formation from megakaryocytes derived from GpIIb/IIIa+ CFU-MK in the presence of hTPO began on day 4 of culture and peaked the following day. On day 5 of culture, lower concentrations of hTPO expanded the number of megakaryocytes, increased the number of proplatelets and the percentage of proplatelet-developing megakaryocytes. Increasing hTPO concentrations resulted in a modest decrease in proplatelet development. We next used hTPO to derive immature or mature megakaryocytes from GpIIb/IIIa+ CFU-MK. These populations of cultured megakaryocytes spontaneously formed proplatelets when recultured in the absence of exogenous hTPO. The addition of hTPO at higher concentrations modestly augmented proplatelet production from immature megakaryocytes derived from 2-day liquid cultures. However, either murine interleukin-6 (IL-6) or human IL-11, but not rat IL-3, was more potent than hTPO in augmenting proplatelet formation from immature megakaryocytes. Each of these four cytokines had an inhibitory effect on proplatelet formation from more differentiated megakaryocytes derived from 3-day liquid cultures. These results indicate that TPO enhances proplatelet production primarily by stimulating CFU-MK to increase the number of proplatelet-forming megakaryocytes and that its action is clearly different from those of other cytokines that also stimulate megakaryocytopoiesis.

Original languageEnglish
Pages (from-to)169-176
Number of pages8
JournalExperimental Hematology
Volume25
Issue number2
Publication statusPublished - 1997 Mar 13
Externally publishedYes

Keywords

  • GpIIb/IIIa
  • megakaryocyte
  • megakaryocyte progenitor cell
  • proplatelet
  • thrombopoietin

ASJC Scopus subject areas

  • Molecular Biology
  • Hematology
  • Genetics
  • Cell Biology
  • Cancer Research

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    Horie, K., Miyazaki, H., Hagiwara, T., Tahara, E., Matsumoto, A., Kadoya, T., Ogami, K., & Kato, T. (1997). Action of thrombopoietin at the megakaryocyte progenitor level is critical for the subsequent proplatelet production. Experimental Hematology, 25(2), 169-176.