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SH Zuckerman, YM Surprenant and J Tang
Department of Immunology, Lilly Research Labs, Indianapolis, IN 46285.
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.
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