Differential effects of human granulocyte colony-stimulating factor (hG-CSF) and thrombopoietin on megakaryopoiesis and platelet function in hG-CSF receptor-transgenic mice.
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.
Yang
F C
FC
Department of Clinical Oncology and the Department of Molecular and Developmental Biology, The Institute of Medical Science, The University of Tokyo, Japan.
Tsuji
K
K
Oda
A
A
Ebihara
Y
Y
Xu
M J
MJ
Kaneko
A
A
Hanada
S
S
Mitsui
T
T
Kikuchi
A
A
Manabe
A
A
Watanabe
S
S
Ikeda
Y
Y
Nakahata
T
T
D000818:Animals; D001792:Blood Platelets / Q000166:cytology / Q000502:physiology*; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D018014:Gene Transfer Techniques; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D006410:Hematopoiesis / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D008533:Megakaryocytes / Q000166:cytology / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D015539:Platelet Activation / Q000187:drug effects / Q000502:physiology; D016188:Receptors, Granulocyte Colony-Stimulating Factor / Q000502:physiology*
D016188:Receptors, Granulocyte Colony-Stimulating Factor; D016179:Granulocyte Colony-Stimulating Factor