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Hematopoietic and lymphopoietic responses in human granulocyte-macrophage colony-stimulating factor (GM-CSF) receptor transgenic mice injected with human GM-CSF
Author(s): Nishijima I, Nakahata T, Watanabe S, Tsuji K, Tanaka I, Hirabayashi Y, Inoue T, Arai K
Source: BLOOD    Volume: 90    Issue: 3    Pages: 1031-1038    Published: AUG 1 1997  
Times Cited: 18     References: 27     
Abstract: Using a clonal assay of bone marrow (BM) cells from transgenic mice (Tg-mice) expressing the human granulocyte-macrophage colony-stimulating factor receptor (hGM-CSFR), we found in earlier studies that hGM-CSF alone supported the development not only of granulocyte-macrophage colonies, but also of erythrocytes, megakaryocytes, mast cells, blast cells, and mixed hematopoietic colonies, In this report, we evaluated the in vivo effects of hGM-CSF on hematopoietic and lymphopoietic responses in the hGM-CSFR Tg-mice, Administration of this factor to Tg-mice resulted in dose-dependent increases in numbers of reticulocytes and white blood cells (WBCs) in the peripheral blood, Morphological analysis of WBCs showed that the numbers of all types of the cell, including neutrophils, eosinophils, monocytes, and lymphocytes increased; the most remarkable being in lymphocytes that contained a number of large granular lymphocytes (LGLs) in addition to mature T and B cells. However, total cellularity of the BM of the Tg-mice decreased in a dose-dependent manner when hGM-CSF was injected, In sharp contrast to the BM, spleens of the Tg-mice were grossly enlarged. Although all types of blood cells and hematopoietic progenitors increased in the spleen, erythroid cells and their progenitors showed the most significant increase. Increased numbers of megakaryocytes and LGLs were also observed in spleen and liver of the treated Tg-mice. Flow cytometric analysis showed that LGLs expanded in Tg-mice expressed Mac-1(+)CD3(-)NK1.1(+). The thymus of Tg-mice treated with hGM-CSF exhibited a dose-dependent shrinkage and a remarkable decrease in CD4(+)CD8(+) cells, Thus, hGM-CSF stimulated not only myelopoiesis but also erythropoiesis and megakaryopoiesis of hGM-CSFR Tg-mice in vivo, in accordance with our reported in vitro findings. In addition, hGM-CSF affected the development of lymphoid cells, including natural killer cells of these Tg-mice. (C) 1997 by The American Society of Hematology.
Document Type: Article
Language: English
Addresses:
1. UNIV TOKYO, INST MED SCI, DEPT MOL & DEV BIOL, DEPT CLIN ONCOL, MINATO KU, TOKYO 108, JAPAN
2. NATL INST HLTH SCI, DEPT TOXICOL, TOKYO 158, JAPAN
Publisher: W B SAUNDERS CO, INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399
Subject Category: Hematology
IDS Number: XN126
ISSN: 0006-4971
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