Synergistic effects of IL-4 and either GM-CSF or IL-3 on the induction of CD23 expression by human monocytes: regulatory effects of IFN-alpha and IFN-gamma.
CD23 expression by B cells and monocytes can be regulated by cytokines including IL-4, IFN-gamma and IFN-alpha. We recently reported that GM-CSF and IL-3 are also capable of regulating CD23 expression, with GM-CSF enhancing CD23 expression by monocytes and IL-3 enhancing CD23 expression by both monocytes and B cells. In this study, we have assessed the effect of combinations of cytokines on monocyte CD23 expression. IL-4 acted in a synergistic manner with either GM-CSF or IL-3 to induce monocyte CD23 expression. Interestingly, culture of monocytes with GM-CSF, IL-3 or IL-4 resulted in two subpopulations of cells, one negative or dull for surface CD23 and the other expressing relatively high levels of CD23. In contrast, culturing monocytes in the combination of IL-4 with either GM-CSF or IL-3 resulted in a single population of cells expressing very high levels of CD23. The synergy between IL-4 and either GM-CSF or IL-3 was also reflected at the level of release of soluble CD23 and CD23 mRNA expression and was seen at both sub-optimal and optimal cytokine concentrations. GM-CSF, IL-3 and IL-4 all enhanced monocyte expression of class II MHC, though no additive or synergistic effects were seen with cytokine combinations. IFN-gamma failed to induce monocyte CD23 expression when acting alone, though it enhanced both surface and soluble CD23 when acting in the presence of GM-CSF, IL-3 or IL-4. In contrast, IFN-alpha was a potent inhibitor of monocyte CD23 expression induced by these three cytokines.(ABSTRACT TRUNCATED AT 250 WORDS)
Alderson
M R
MR
Department of Cellular Immunology, Immunex Research and Development Corporation, Seattle, WA 98101.
Armitage
R J
RJ
Tough
T W
TW
Ziegler
S F
SF
D002478:Cells, Cultured; D016207:Cytokines / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D004357:Drug Synergism; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006684:HLA-DR Antigens / Q000097:blood; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology; D007371:Interferon-gamma / Q000494:pharmacology; D007377:Interleukin-3 / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology; D009000:Monocytes / Q000187:drug effects* / Q000276:immunology; D017455:Receptors, IgE / Q000096:biosynthesis*; D012995:Solubility
D016207:Cytokines; D006684:HLA-DR Antigens; D016898:Interferon-alpha; D007377:Interleukin-3; D017455:Receptors, IgE; D015847:Interleukin-4; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor