Augmentation of megakaryocytopoiesis within the hematopoietic microenvironment of human granulocyte colony-stimulating factor transgenic mice

• Published in: Experimental hematology 2001-08, Vol.29 (8), p.1010-1018
• Main Authors: Fujita, Tohru, Yamada, Taketo, Hashiguchi, Akinori, Fukushima, Sachiko, Kondoh, Kensuke, Fujimoto, Jun-ichiroh, Hata, Jun-ichi
• Format: Article
• Language: English
• Subjects: Animals; Bone Marrow Cells - cytology; Bone Marrow Transplantation - pathology; Bone Marrow Transplantation - physiology; Cell Differentiation - drug effects; Colony-Forming Units Assay; Crosses, Genetic; Granulocyte Colony-Stimulating Factor - genetics; Granulocyte Colony-Stimulating Factor - physiology; Hematopoiesis - genetics; Hematopoiesis - physiology; Humans; Interleukin-11 - pharmacology; Megakaryocytes - cytology; Megakaryocytes - drug effects; Megakaryocytes - ultrastructure; Mice; Mice, Inbred C57BL; Mice, Transgenic; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - genetics; Spleen - cytology; Thrombopoietin - pharmacology; Transcription, Genetic
• ISSN: 0301-472X; 1873-2399
• DOI: 10.1016/S0301-472X(01)00672-5

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. 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. 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. 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.