Optimal proliferation of a hematopoietic progenitor cell line requires either costimulation with stem cell factor or increase of receptor expression that can be replaced by overexpression of Bcl-2

Huei Mei Huang, Jian Chiuan Li, Yueh Chun Hsieh, Hsin Fang Yang-Yen, Jeffrey Jong Young Yen

研究成果: 雜誌貢獻文章同行評審

16 引文 斯高帕斯(Scopus)

摘要

In vitro proliferation of hematopoietic stem cells requires costimulation by multiple regulatory factors whereas expansion of lineage- committed progenitor cells generated by stem cells usually requires only a single factor. The distinct requirement of factors for proliferation coincides with the differential temporal expression of the subunits of cytokine receptors during early stem cell differentiation. In this study, we explored the underlying mechanism of the requirement of costimulation in a hematopoietic progenitor cell line TF-1. We found that granulocyte-macrophage colony-stimulating factor (GM-CSF) optimally activated proliferation of TF-1 cells regardless of the presence or absence of stem cell factor (SCF). However, interleukin-5 (IL-5) alone sustained survival of TF-1 cells and required costimulation of SCF for optimal proliferation. The synergistic effect of SCF was partly due to its anti-apoptosis activity. Overexpression of the IL-5 receptor α subunit (IL5Rα) in TF-1 cells by genetic selection or retroviral infection also resumed optimal proliferation due to correction of the defect in apoptosis suppression. Exogenous expression of an oncogenic anti-apoptosis protein, Bcl-2, conferred on TF-1 cells an IL-5-dependent phenotype. In summary, our data suggested SCF costimulation is only necessary when the expression level of IL5Rα is low and apoptosis suppression is defective in the signal transduction of IL-5. Expression of BCl-2 proteins released the growth restriction of the progenitor cells and may be implicated in leukemia formation.

原文英語
頁(從 - 到)2569-2577
頁數9
期刊Blood
93
發行號8
DOIs
出版狀態已發佈 - 四月 15 1999
對外發佈

ASJC Scopus subject areas

  • 生物化學
  • 免疫學
  • 血液學
  • 細胞生物學

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