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Vol. 133, No. 3, 2004
Issue release date: March 2004
Int Arch Allergy Immunol 2004;133:305–315

Fcγ Receptors on Mast Cells: Activatory and Inhibitory Regulation of Mediator Release

Tkaczyk C. · Okayama Y. · Metcalfe D.D. · Gilfillan A.M.
aLaboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Md., USA; bLaboratory of Allergy Transcriptome, Research Center for Allergy and Immunology, RIKENYokohama Institute, Yokohama, Japan

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Mast cell activation and subsequent release of proinflammatory mediators are primarily a consequence of aggregation of the high affinity receptors for IgE (FcεRI) on the mast cell surface following antigen-dependent ligation of FcεRI-bound IgE. However, data obtained from rodent and human mast cells have revealed that IgG receptors (FcγR) can both promote and inhibit mast cell activation. These responses appear to be species and/or mast cell phenotype dependent. In CD34+-derived human mast cells exposed to interferon-γ, FcγRI is upregulated, FcγRII is expressed but not upregulated, and FcγRIII is not expressed. In contrast, in mouse mast cells, FcγRII and FcγRIII receptors are expressed, whereas FcγRI is not. Aggregation of FcγRI on human mast cells promotes mediator release in a manner generally similar to that observed following FcεRI aggregation. Aggregation of FcγRIIb in mouse mast cells fails to influence cellular processes; however, when coligated with FcεRI, signaling events thus activated downregulate antigen-dependent mediator release. These divergent responses are a consequence of different motifs contained within the cytosolic tails of the signaling subunits of these receptors and the specific signaling molecules recruited by these receptors following ligation. The studies described imply that data obtained in rodent models regarding the influence of FcγRs on mast cells may not be directly translatable to the human. The exploitation of FcγRs for a potential therapy for the treatment of allergic disorders is discussed in this context.

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