Augmentation of megakaryocytopoiesis within the hematopoietic microenvironment of human granulocyte colony-stimulating factor transgenic mice.
OBJECTIVE
Megakaryocytopoiesis was dramatically augmented in human granulocyte colony-stimulating factor transgenic mice (G-Tg) compared to littermates. We examined the characteristics of megakaryocytes and megakaryocyte progenitor cells in these mice.


METHODS
The numbers of colony-forming unit megakaryocytes (CFU-MK) and megakaryocytes in hematopoietic organs were counted. The megakaryocytes of G-Tg were examined ultrastructurally, and bone marrow transplantation studies using congenic G-Tg (Ly5.2) and C57BL/6 (Ly5.1) were performed. The number of day-14 colony-forming unit spleen (CFU-S) that contained megakaryocytes in [Ly5.1 > G-Tg] and [G-Tg > Ly5.1] mice also was counted.


RESULTS
The number of CFU-MK increased markedly in the spleen, bone marrow, and peripheral blood. The number of megakaryocytes in the spleen and bone marrow also were increased in G-Tg mice. Ultrastructural analyses revealed that megakaryocytes in G-Tg mice were immature. Bone marrow transplantation studies of [Ly5.1 > G-Tg] mice resulted in a significantly increased number of megakaryocytes compared to [G-Tg > Ly5.1] mice. The number of day-14 CFU-S that contained megakaryocytes was increased markedly in [Ly5.1 > G-Tg] mice compared to [G-Tg > Ly5.1] mice. In vitro differentiation of megakaryocytes in [Ly5.1 > G-Tg] mice was induced by interleukin-11 and thrombopoietin.


CONCLUSIONS
The results showed that the hematopoietic marrow microenvironment of G-Tg is important in augmenting megakaryocytopoiesis. [Ly5.1 > G-Tg] mice are potentially useful as a source of murine megakaryocytes and their progenitors.
Fujita
T
T
Department of Pathology, Keio University School of Medicine, Tokyo, Japan.
Yamada
T
T
Hashiguchi
A
A
Fukushima
S
S
Kondoh
K
K
Fujimoto
J
J
Hata
J
J
D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology; D016026:Bone Marrow Transplantation / Q000473:pathology / Q000502:physiology*; D002454:Cell Differentiation / Q000187:drug effects; D003114:Colony-Forming Units Assay; D003433:Crosses, Genetic; D016179:Granulocyte Colony-Stimulating Factor / Q000235:genetics* / Q000502:physiology*; D006410:Hematopoiesis / Q000235:genetics / Q000502:physiology*; D006801:Humans; D017370:Interleukin-11 / Q000494:pharmacology; D008533:Megakaryocytes / Q000166:cytology* / Q000187:drug effects / Q000648:ultrastructure; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013154:Spleen / Q000166:cytology; D013926:Thrombopoietin / Q000494:pharmacology; D014158:Transcription, Genetic
D017370:Interleukin-11; D012333:RNA, Messenger; D016179:Granulocyte Colony-Stimulating Factor; D013926:Thrombopoietin