Effects of recombinant human colony stimulating factors (CSF) (granulocyte-macrophage CSF, granulocyte CSF, and CSF-1) on human monocyte/macrophage differentiation.
Purified recombinant human granulocyte-macrophage (rhuGM)-CSF, rhuG-CSF, and rhuCSF-1 were evaluated for their capacity to influence the differentiation of U-937 cells and normal human monocytes. The human U-937 cell line represents an early stage of monocytic differentiation. It was found that rhuGM-CSF and rhuG-CSF, but not rhuCSF-1, induced phenotypic changes consistent with monocyte/macrophage differentiation in U-937 cells. After 3 days of culture in the presence of either rhuGM-CSF or rhuG-CSF, a small but significant proportion of U-937 cells were able to reduce nitroblue tetrazolium. Nitroblue tetrazolium reduction, however, was maximally induced when rhuGM-CSF and rhuG-CSF were added in combination. These changes were accompanied by increased alpha-naphthyl acetate esterase activity, acquisition of macrophage morphology, Mo-1 Ag expression, and decreased cell proliferation. rhuGM-CSF alone also induced expression of the c-fms proto-oncogene (CSF-1 receptor) in U-937 cells and this expression was enhanced by the combination of rhuGM-CSF and rhuG-CSF. In cultured normal human peripheral blood monocytes, representing a late stage of maturation, rhuGM-CSF and rhuCSF-1 differentially increased Mo-1 and My-4 Ag expression, respectively, whereas rhuG-CSF was without effect. Our results suggest that the interaction of GM-CSF, G-CSF, and CSF-1 may play a fundamental role in the early and late stages of the human monocyte/macrophage differentiation process.
Geissler
K
K
Department of Medicine, Indiana University School of Medicine, Indianapolis 46223.
Harrington
M
M
Srivastava
C
C
Leemhuis
T
T
Tricot
G
G
Broxmeyer
H E
HE
D000954:Antigens, Surface / Q000032:analysis; D002454:Cell Differentiation; D002455:Cell Division; D002460:Cell Line; D003115:Colony-Stimulating Factors / Q000494:pharmacology*; D016179:Granulocyte Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D006098:Granulocytes / Q000502:physiology*; D006133:Growth Substances / Q000494:pharmacology; D006801:Humans; D008264:Macrophages / Q000502:physiology*; D009000:Monocytes / Q000201:enzymology / Q000378:metabolism / Q000502:physiology*; D009283:Naphthol AS D Esterase / Q000378:metabolism; D009580:Nitroblue Tetrazolium; D010084:Oxidation-Reduction; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000235:genetics; D016186:Receptor, Macrophage Colony-Stimulating Factor; D011994:Recombinant Proteins / Q000494:pharmacology
D000954:Antigens, Surface; D003115:Colony-Stimulating Factors; D006133:Growth Substances; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; D009580:Nitroblue Tetrazolium; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D016186:Receptor, Macrophage Colony-Stimulating Factor; D009283:Naphthol AS D Esterase