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Blood, Vol. 94 No. 3 (August 1), 1999:
pp. 950-958
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, and
Tatsutoshi Nakahata
From the Department of Clinical Oncology and the Department of
Molecular and Developmental Biology, The Institute of Medical Science,
The University of Tokyo; and the Department of Internal Medicine, Keio
University, Tokyo, Japan.
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 hG-CSF 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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