Human granulocyte-macrophage colony-stimulating factor (hGM-CSF)-dependent in vitro and in vivo proliferation and differentiation of all hematopoietic progenitor cells in hGM-CSF receptor transgenic mice

Ichiko Nishijima, Sumiko Watanabe, Tatsutoshi Nakahata, Ken Ichi Arai

研究成果: Article査読

2 被引用数 (Scopus)

抄録

To examine the relation between receptor expression and differentiation of hematopoietic cells, we produced transgenic mice that constitutively expressed the human granulocyte-macrophage colony stimulating factor (hGM-CSF) receptor at almost all stages of hematopoietic cell development. The high-affinity GM-CSF receptor is species specific, allowing analysis of the specific effects of hGM-CSF in our mouse model. Proliferation and differentiation of hematopoietic progenitor cells from transgenic mice were analyzed by means of methylcellulose colony-forming assay and in vivo treatment with hGM-CSF, respectively. We found that hGM-CSF supported various types of colonies, including granulocyte-macrophage, mast cell, megakaryocyte, blast cell, and mixed hematopoietic colonies, whereas mouse GM-CSF supported only granulocyte-macrophage colonies. In addition, hGM-CSF generated erythrocyte colonies in the absence of erythropoietin. Furthermore, in vivo administration of hGM-CSF to transgenic mice resulted in a dose-dependent increase in reticulocytes and white blood cells in the peripheral blood. The spleens of the mice showed gross enlargement, mainly caused by an increase of erythroid cells and their progenitors. Taken together, these results indicate that hGM-CSF receptor-mediated signals can support the growth of cells of all hematopoietic cell lineages if this receptor is present on the cell surface. This implies that the differentiation of hematopoietic progenitor cells is not determined by exogenous cytokine stimulation (instruction model) but by an intrinsic cell program in which cytokines simply select cells that express the appropriate receptor (stochastic model).

本文言語English
ページ(範囲)S79-S86
ジャーナルJournal of Allergy and Clinical Immunology
100
6 SUPPL.
DOI
出版ステータスPublished - 1997
外部発表はい

ASJC Scopus subject areas

  • 免疫アレルギー学
  • 免疫学

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