title: IFN-alpha and IFN-gamma have different regulatory effects on IL-4-induced membrane expression of Fc epsilon RIIb and release of soluble Fc epsilon RIIb by human monocytes.
abstract: We used highly purified human monocytes to study the regulation of cell surface and secretion of the low affinity FcR for IgE (Fc epsilon RIIb). IL-4 induces Fc epsilon RIIb expression and soluble Fc epsilon RIIb release in a dose-dependent manner. Significant levels of Fc epsilon RIIb expression were obtained after 12 h of incubation with IL-4 and maximal expression was observed between 24 to 48 h after which the expression declined. Surface expression was followed by secretion of soluble Fc epsilon RIIb which reached maximal levels after 3 to 4 days of incubation and which remained constant throughout 7 days of culture. Induction of Fc epsilon RIIb expression by IL-4 was completely blocked by anti-IL-4 antibodies. Furthermore, IL-1 alpha, IL-2, IL-5, granulocyte-macrophage-CSF, IFN-alpha, IFN-gamma, low m.w. BCGF and also LPS all failed to induce Fc epsilon RIIb expression, demonstrating the specificity of the induction. Fc epsilon RIIb membrane expression induced by IL-4 was reduced in the presence of IFN-gamma and IFN-alpha. Strong inhibition of IL-4-induced Fc epsilon RIIb expression was observed at IFN-alpha concentrations of 450 U/ml (80%), and 100 U/ml of IFN-gamma reduced IL-4-induced Fc epsilon RIIb expression by 70%. Interestingly, soluble Fc epsilon RIIb release was strongly inhibited by IFN-alpha. In contrast, IFN-gamma did not affect soluble Fc epsilon RIIb release, suggesting that reduced membrane expression of Fc epsilon RIIb observed in the presence of IFN-gamma does not reflect inhibition of Fc epsilon RIIb expression but may represent enhanced cleavage or reduced anchoring in the membrane of Fc epsilon RIIb. Finally, IL-5 that has been shown to enhance IL-4-induced Fc epsilon RII on B cells does not enhance significantly IL-4-induced Fc epsilon RIIb membrane expression or subsequent soluble Fc epsilon RIIb release by monocytes. Taken together these results show that IFN-alpha and IFN-gamma have different regulatory effects on IL-4-induced Fc epsilon RIIb membrane expression and soluble Fc epsilon RIIb release by human monocytes.
authors: Division of Immunology, The Netherlands Cancer Institute, Amsterdam.
authors: A A
authors: AA
authors: te Velde
authors: F
authors: F
authors: Rousset
authors: C
authors: C
authors: Peronne
authors: J E
authors: JE
authors: De Vries
authors: C G
authors: CG
authors: Figdor
mesh_terms: D000944:Antigens, Differentiation, B-Lymphocyte / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D005434:Flow Cytometry; D006801:Humans; D066298:In Vitro Techniques; D007370:Interferon Type I / Q000494:pharmacology*; D007371:Interferon-gamma / Q000494:pharmacology*; D015847:Interleukin-4 / Q000494:pharmacology*; D015848:Interleukin-5 / Q000494:pharmacology; D007700:Kinetics; D009000:Monocytes / Q000276:immunology* / Q000378:metabolism; D011961:Receptors, Fc / Q000378:metabolism*; D017455:Receptors, IgE; D011994:Recombinant Proteins; D012995:Solubility
chemical_list: D000944:Antigens, Differentiation, B-Lymphocyte; D007370:Interferon Type I; D015848:Interleukin-5; D011961:Receptors, Fc; D017455:Receptors, IgE; D011994:Recombinant Proteins; D015847:Interleukin-4; D007371:Interferon-gamma