Differential effects of human granulocyte colony-stimulating factor (hG- CSF) and thrombopoietin on megakaryopoiesis and platelet function in hG-CSF receptor-transgenic mice

Feng-Chun Yang, Kohichiro Tsuji, Atsushi Oda, Yasuhiro Ebihara, Mingjiang Xu, Azusa Kaneko, Sachiyo Hanada, Tetsuo Mitsui, Akira Kikuchi, Atsushi Manabe, Sumiko Watanabe, Yasuo Ikeda, Tatsutoshi Nakahata

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Abstract

Granulocyte-colony stimulating factor (G-CSF) has been found to act on the neutrophilic lineage. We recently showed that human G-CSF (hG-CSF) has effects similar to early-acting cytokines such as interleukin-3 (IL-3) in the development of multipotential hematopoietic progenitors in transgenic (Tg) mice expressing receptors (R) for hG-CSF. In the present study, we examined the effects of hG-CSF on more mature hematopoietic cells committed to megakaryocytic lineage in these Tg mice. The administration of hG-CSF to the Tg mice increased the numbers of both platelets in peripheral blood and megakaryocytes in the spleen, indicating that hG-CSF stimulates megakaryopoiesis in the Tg mice in vivo. The stimulatory effect of hG-CSF was also supported by the results of studies in vitro, hG-CSF supported megakaryocyte colony formation in a dose-dependent fashion in clonal cultures of bone marrow cells derived from the Tg mice. Direct effects of hG-CSF on megakaryocytic progenitors in the Tg mice were confirmed by culture of single-cell sorted from bone marrow cells, hG-CSF showed a stronger effect on maturation of megakaryocytes in the Tg mice than that of IL-3 alone, but weaker than that of TPO alone. In addition, hG-CSF induced phosphorylation of STAT3 but not Jak2 or STAT5, while TPO induced phosphorylation of both. In contrast to TPO, hG-CSF did not enhance ADP-induced aggregation. Thus, hG-CSF has a wide variety of functions in megakaryopoiesis of hG-CSFR-Tg mice, as compared with other megakaryopoietic cytokines, but the activity of hGCSF in megakaryocytes and platelets does not stand up to a comparison with that of TPO. Specific signals may be required for the full maturation and activation of platelets.

Original languageEnglish (US)
Pages (from-to)950-958
Number of pages9
JournalBlood
Volume94
Issue number3
StatePublished - Aug 1 1999
Externally publishedYes

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ASJC Scopus subject areas

  • Hematology

Cite this

Yang, F-C., Tsuji, K., Oda, A., Ebihara, Y., Xu, M., Kaneko, A., Hanada, S., Mitsui, T., Kikuchi, A., Manabe, A., Watanabe, S., Ikeda, Y., & Nakahata, T. (1999). Differential effects of human granulocyte colony-stimulating factor (hG- CSF) and thrombopoietin on megakaryopoiesis and platelet function in hG-CSF receptor-transgenic mice. Blood, 94(3), 950-958.