Synergistic effect of granulocyte-macrophage colony-stimulating factor and 1,25-dihydroxyvitamin D3 on the differentiation of the human monocytic cell line U937.
The human monoblastlike cell line U937 can be induced to differentiate by a variety of agents including gamma-interferon, phorbol esters, retinoic acid, and 1,25-dihydroxyvitamin D3 (VD3). Incubation of U937 with 1 to 1,000 units of recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF) did not induce macrophage differentiation. A synergistic effect on macrophage differentiation was observed, however, when U937 was cocultured with 10(-8) mol/L VD3 plus 50 U/mL GM-CSF. GM-CSF-plus VD3-treated cells demonstrated significant increases in OKM1 antigen expression, increased chemokinesis and chemotaxis, and increased Fc receptor-mediated erythrophagocytosis. Human peripheral blood monocyte cultures also demonstrated increased OKM1 antigen expression and chemotaxis when incubated with 50 to 500 U/mL of GM-CSF for 48 to 72 hours. VD3, however, was not necessary for the increases in effector function observed for GM-CSF-stimulated monocyte cultures. In distinction to the synergistic effect of GM-CSF on VD3-induced differentiation of U937, recombinant human granulocyte colony-stimulating factor (G-CSF) at comparable concentrations had no augmenting effect over that observed for VD3 alone. These results suggest that GM-CSF, in the presence of other physiological stimuli, can induce significant phenotypic changes in GM-CSF-nonresponsive cells of the monocytic lineage and can increase the effector functions of GM-CSF-responsive peripheral blood monocyte cultures.
Zuckerman
S H
SH
Department of Immunology, Lilly Research Labs, Indianapolis, IN 46285.
Surprenant
Y M
YM
Tang
J
J
D000954:Antigens, Surface / Q000032:analysis; D002117:Calcitriol / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D002633:Chemotaxis / Q000187:drug effects; D003115:Colony-Stimulating Factors / Q000494:pharmacology*; D004357:Drug Synergism; D004912:Erythrocytes; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D006133:Growth Substances / Q000494:pharmacology*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000166:cytology* / Q000276:immunology; D010587:Phagocytosis / Q000187:drug effects; D011961:Receptors, Fc / Q000502:physiology
D000954:Antigens, Surface; D003115:Colony-Stimulating Factors; D006133:Growth Substances; D011961:Receptors, Fc; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D002117:Calcitriol