Apoptosis of hemopoietic cells by the human granulocyte-macrophage colony-stimulating factor mutant E21R

作者：Iversen PO; To LB; Lopez AF

来源：Proceedings of the National Academy of Sciences of the United States of America, 1996, 93(7): 2785-2789.

DOI：10.1073/pnas.93.7.2785

• cell death
• cytokines
• progenitor cells
• leukemia
• receptors

Human granulocyte-macrophage colony-stimulating factor (GM-CSF) binds to a high-affinity heterodimeric receptor composed of a specific cu chain and a common beta chain (beta(c)), which is shared with the receptors for interleukins 3 and 5, Hemopoietic cell survival requires GM-CSF binding this high-affinity receptor, We have recently developed the GM-CSF mutant E21R, which selectively binds to the cu chain and behaves as a competitive GM-CSF antagonist, We have now examined the role of E21R on the survival of hemopoietic cells and found that E21R causes apoptosis (programmed cell death) of normal and malignant cells directly in the absence of GM-CSF. The direct apoptotic effect of E21R occurred in a dose- and time-dependent manner, Apoptosis by E21R was dependent on cells expressing the high-affinity GM-CSF receptor and could be blocked by GM-CSF. Significantly, apoptosis of the cells occurred even in the presence of the survival factors granulocyte CSF and stem cell factor but was prevented by engagement of beta(c) with interleukin 3, The initiation of apoptosis required phosphorylation, transcriptional activity, and protein synthesis, These findings support a model whereby binding of E21R to the cu chain leads to

• 出版日期1996-4-2
• 单位河北医科大学