Granulocyte-macrophage colony stimulating factor (GM-CSF) is a hematopoietic growth factor involved in the generation of granulocytes, macrophages, and dendritic cells from hematopoietic stem cells. The GM-CSF receptor is a heterodimer of the GM-CSF receptor α subunit and the β subunit which is not directly involved in binding GM-CSF. GM-CSF is used clinically in the field of oncology and hematology. Recently we have identified GM-CSF as a neuronal growth factor in the brain which counteracts apoptosis, and reduces infarct size in stroke models in vivo. GM-CSF has also been identified as a factor involved in arteriogenesis after brain ischemia. GM-CSF is therefore the third hematopoietic factor after EPO and G-CSF that has functions in the brain.
GM-CSF was first identified in mouse lung tissue-conditioned medium following lipopolysaccharide injection into mice by its ability to stimulate proliferation of mouse bone marrow cells in vitro and generate colonies of both granulocytes and macrophages. Much has been learned about the hematopoietic promoting effect of this heavily glycosylated cytokine. GM-CSF stimulates multipotent progenitor cells depending on its concentration, the proliferation of macrophage progenitors at the lowest doses, followed by granulocyte, erythroid, eosinophil, megakaryocyte and multipotent progenitors. It also stimulates the differentiation of myeloid leukemic cellsand controls eosinophil function in some instances.
It is uncovered that the hematopoietic factor GM-CSF is also a neuronal growth factor with strong anti-apoptotic actions on neurons. On neuroepithelial cells from embryonic mouse brains. Addition of GM-CSF at concentrations of 0.05 to 5 μg/ml for 48 h inhibited staurosporine-induced apoptosis, and increased the number and diameter of stem cell colonies. With addition of 0.5 μg/ml GM-CSF for 48 h the authors report a diminished number of MAP-2 and GFAP positivecells, indicating a potential negative impact of GM-CSF on (neuronal) differentiation. In general these data from the embryo support our findings on adult neural stem cells, with regard to presence of the receptor on neural stem cells, and anti-apoptotic actions of GM-CSF.
It is shown that GM-CSF receptor is expressed on adult neural stem cells, and that GM-CSF induces dose-dependent neuronal differentiation of these cells. This property places GM-CSF together with other hematopoietic factors that have recently been shown to function also as growth factors in the brain. On hematopoietic stem cells, GM-CSF induces the generation and maturation of neutrophilic granulocytes and monocytes/ macrophages. A similar role of GM-CSF in hematopoietic and neural differentiation underlines the similarities that exist between the two stem cell populations.
• Krüger C, Laage R, Pitzer C, et al. The hematopoietic factor GM-CSF (granulocyte-macrophage colony-stimulating factor) promotes neuronal differentiation of adult neural stem cells in vitro[J]. BMC neuroscience, 2007, 8(1): 88.
• Shi Y, Liu C H, Roberts A I, et al. Granulocyte-macrophage colony-stimulating factor (GM-CSF) and T-cell responses: what we do and don't know[J]. Cell research, 2006, 16(2): 126-133.