Megakaryocytic maturation is regulated by maintaining a balance against cytokine induced-cell proliferation: Steel factor retards thrombopoietin-induced megakaryocytic differentiation while synergistically stimulating mitogenesis

K. Miyazawa, J. Nishimaki, T. Katagiri, M. Yaguchi, O. Iwase, A. Gotoh, T. Tauchi, Y. Kawanishi, K. Toyama, K. Ohyashiki, T. Ishibashi, H. E. Broxmeyer

Research output: Contribution to journalArticle

4 Scopus citations

Abstract

Using a factor-dependent cell line MO7ER, which contains a stably transduced human erythropoietin (EPO) receptor gene in human megakaryoblastic cell line MO7e and which resulted in concomitant expression of EPO receptor, c-Mpl and c-Kit, we investigated the biological effects of these cytokines in terms of cell growth and differentiation. Thrombopoietin (TPO), EPO and Steel factor (SLF) all stimulated MO7ER cell proliferation in a dose-dependent manner. Combined stimulation of cells with SLF plus either TPO or EPO resulted in striking synergistic enhancement of MO7ER cell growth as compared with each cytokine alone, whereas combination of TPO plus EPO showed only an additive effect on cell proliferation. With regards to cell differentiation, either TPO or EPO treatment induced enhancement of platelet glycoprotein (GP) IIb/IIIa and GPIb expression. SLF induced GPIIb/IIIa and GPIb expression, but the effect was much weaker than that of EPO or TPO. However, addition of SLF to either TPO- or EPO-containing cultures (which induced potent mitogenesis in MO7ER cells) resulted in suppression of these megakaryocyte specific antigens. Addition of low-dose cytosine arabinoside (Ara-C)(1 to 10 ng/ml) enhanced TPO- or EPO- induced megakaryocytic differentiation in MO7ER cells while mildly suppressing cell growth. Treatment the cells with low-dose Ara-C plus TPO plus SLF overrode the proliferative enhancing effects of SLF and induced GPIIb/IIIa and GPIb expression as efficient as.

Original languageEnglish (US)
Pages (from-to)233-246
Number of pages14
JournalHematology
Volume5
Issue number3
DOIs
StatePublished - Jan 1 2000
Externally publishedYes

Keywords

  • Cell growth
  • Differentiation
  • Erythropoietin
  • Hematopoiesis
  • Steel factor
  • Thrombopoietin

ASJC Scopus subject areas

  • Hematology

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