Up-regulation of gamma interferon receptors on the human monocytic cell line U937 by 1,25-dihydroxyvitamin D3 and granulocyte-macrophage colony stimulating factor.
The human monoblast-like cell line U937 can be induced to differentiate by a variety of agents including phorbol esters, retinoic acid, gamma interferon (IFN gamma), and 1,25-dihydroxyvitamin D3 (VD3). Increased expression of OKM1 antigen, Fc receptors, and other cell surface antigens occur with the differentiation of this cell line along the macrophage lineage. Whereas 10(-8) M VD3 alone induces changes in cell surface antigens, there were no changes in the number or affinity of IFN gamma receptors. Incubation of U937 with VD3 and 100 U/ml of granulocyte-macrophage colony-stimulating factor (GM-CSF) resulted in further increases in OKM1 antigen expression and an up-regulation of IFN gamma receptors. The number of IFN gamma receptors increased between two- and fourfold and was maximal after 48 h incubation with VD3 and GM-CSF. Scatchard analysis revealed a single class of receptors before or after differentiation, although the increase in receptor number was associated with an overall decrease in receptor-binding affinity. Incubation of U937 with VD3 plus GM-CSF and IFN gamma resulted in further increases in the density of OKM1 antigen expressed per cell. This increase in OKM1 expression was greater than that observed for U937 incubated with VD3 and GM-CSF or VD3 and IFN gamma alone. These results suggest that GM-CSF up-regulates IFN gamma receptors on VD3-stimulated U937 and enables these cells to be induced further along the pathway of macrophage differentiation, possibly by subsequent interaction with additional cytokines such as IFN gamma.
Zuckerman
S H
SH
Department of Immunology, Lilly Research Labs, Indianapolis, Indiana 46285.
Schreiber
R D
RD
D000943:Antigens, Differentiation / Q000032:analysis; D002117:Calcitriol / Q000494:pharmacology*; D002460:Cell Line; D003115:Colony-Stimulating Factors / Q000494:pharmacology*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D006133:Growth Substances / Q000494:pharmacology*; D006801:Humans; D009000:Monocytes / Q000187:drug effects* / Q000276:immunology; D011971:Receptors, Immunologic / Q000032:analysis / Q000187:drug effects*; D017471:Receptors, Interferon
D000943:Antigens, Differentiation; D003115:Colony-Stimulating Factors; D006133:Growth Substances; D011971:Receptors, Immunologic; D017471:Receptors, Interferon; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D002117:Calcitriol