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, Ming Jiang Xu, Azusa Kaneko, Sachiyo Hanada, Tetsuo Mitsui, Akira Kikuchi, Atsushi Manabe, Sumiko Watanabe, Yasuo Ikeda, Tatsutoshi Nakahata

Research output: Contribution to journalArticle

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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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Granulocyte Colony-Stimulating Factor Receptors
Thrombopoietin
Granulocyte Colony-Stimulating Factor
Platelets
Transgenic Mice
Blood Platelets
Megakaryocytes
Phosphorylation
Interleukin-3
Cell culture
Bone Marrow Cells
Bone
Cells
Cytokines
Platelet Activation
Platelet Count

ASJC Scopus subject areas

  • Hematology

Cite this

Differential effects of human granulocyte colony-stimulating factor (hG- CSF) and thrombopoietin on megakaryopoiesis and platelet function in hG-CSF receptor-transgenic mice. / Yang, Feng Chun; Tsuji, Kohichiro; Oda, Atsushi; Ebihara, Yasuhiro; Xu, Ming Jiang; Kaneko, Azusa; Hanada, Sachiyo; Mitsui, Tetsuo; Kikuchi, Akira; Manabe, Atsushi; Watanabe, Sumiko; Ikeda, Yasuo; Nakahata, Tatsutoshi.

In: Blood, Vol. 94, No. 3, 01.08.1999, p. 950-958.

Research output: Contribution to journalArticle

Yang, FC, Tsuji, K, Oda, A, Ebihara, Y, Xu, MJ, 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, vol. 94, no. 3, pp. 950-958.
Yang, Feng Chun ; Tsuji, Kohichiro ; Oda, Atsushi ; Ebihara, Yasuhiro ; Xu, Ming Jiang ; Kaneko, Azusa ; Hanada, Sachiyo ; Mitsui, Tetsuo ; Kikuchi, Akira ; Manabe, Atsushi ; Watanabe, Sumiko ; Ikeda, Yasuo ; Nakahata, Tatsutoshi. / Differential effects of human granulocyte colony-stimulating factor (hG- CSF) and thrombopoietin on megakaryopoiesis and platelet function in hG-CSF receptor-transgenic mice. In: Blood. 1999 ; Vol. 94, No. 3. pp. 950-958.
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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.",
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AU - Yang, Feng Chun

AU - Tsuji, Kohichiro

AU - Oda, Atsushi

AU - Ebihara, Yasuhiro

AU - Xu, Ming Jiang

AU - Kaneko, Azusa

AU - Hanada, Sachiyo

AU - Mitsui, Tetsuo

AU - Kikuchi, Akira

AU - Manabe, Atsushi

AU - Watanabe, Sumiko

AU - Ikeda, Yasuo

AU - Nakahata, Tatsutoshi

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N2 - 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.

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