Expression of a Functional High-Affinity IgG Receptor, FcγRI, on Human Mast Cells: Up-Regulation by IFN-γ

Okayama, Yoshimichi; Kirshenbaum, Arnold S.; Metcalfe, Dean D.

doi:10.4049/jimmunol.164.8.4332

Cited by 170 publications

(169 citation statements)

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“…The observation that skin mast cells were already sensitized by IgG(T) suggests that free IgG(T) antibodies can bind to high-affinity Fcγ-receptors on equine skin mast cells and that these Fcγ-receptors can activate cellular degranulation. This is similar to the interaction of IgG and the high-affinity FcγRI on human mast cells [21] and differs from binding of IgG to low affinity FcγRII and FcγRIII that requires prior IgG/allergen complex formation [22]. Equine IgG(T) is not an isotype; rather, it represents a fraction of equine IgG composed of IgG3 and IgG5 [31].…”

Section: Discussionmentioning

confidence: 91%

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IgE and IgG antibodies in skin allergy of the horse

et al. 2006

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-In horses, allergies have been characterized by clinical signs and/or intradermal (i.d.) allergen testing. Our aim was to find the first direct evidence that immunoglobulin E (IgE) mediates equine allergy. In addition, we tested the hypothesis that immediate skin reactions in horses can also be mediated by IgG. Anti-IgE affinity columns were used to purify IgE from serum of one healthy horse and three horses affected with summer eczema, an allergic dermatitis which is believed to be induced by Culicoides midges. A modified Prausnitz-Küstner experiment was performed in four clinical healthy horses by i.d. injection of the purified serum IgE antibodies. The following day, Culicoides allergen was injected at the same sites. Skin reactions were not observed in response to allergen alone, and in two horses after stimulation at any previous IgE injection site. However, the other two horses showed an immediate skin reaction at the previous injection sites of IgE obtained from allergic horses. In addition, purified monoclonal antibodies to various equine immunoglobulin isotypes were injected i.d. into six healthy horses. Immediate skin reactions were observed in response to anti-IgE (6/6 horses) and anti-IgG(T) injections (5/6 horses). The specificities of both antibodies for IgE and IgG(T), respectively, were confirmed by enzyme linked immunosorbent assays. The results provide the first direct evidence that IgE mediates classical Type-I allergy in horses and plays a major role in the pathogenesis of summer eczema. The data also suggest that IgG(T) can bind to skin mast cells and might contribute to clinical allergy.horse / allergy / summer eczema / IgE / IgG

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Section: Discussionmentioning

confidence: 91%

“…In other species, IgE antibodies are bound to the high-affinity FcεRI [11]. In humans and rodents, IgG antibodies can also bind to various IgG receptors (FcγRs) on mast cells and activate or inhibit degranulation depending on the receptor [7,21,22]. IgG binding to canine mast cells via Fcγ-receptors has also been reported [23].…”

Section: Discussionmentioning

confidence: 99%

IgE and IgG antibodies in skin allergy of the horse

et al. 2006

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“…Human mast cells constitutively express (h)FcγRIIA on their surface, which mediates positive signaling upon receptor activation [37]. Under certain conditions, such as stimulation with IFN-γ, human mast cells can also express hFcγRI that promotes degranulation and mRNA expression for specific cytokines, including TNF-α, GM-CSF, IL-3, and IL-13 [38]. Mouse mast cells express FcγRIIB (inhibitory) and FcγRIII (activating).…”

Section: Signaling In Fcγrs-induced Activationmentioning

confidence: 99%

Mast cell activation: A complex interplay of positive and negative signaling pathways

Sibilano¹,

2014

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Mast cells regulate the immunological responses causing allergy and autoimmunity, and contribute to the tumor microenvironment through generation and secretion of a broad array of preformed, granule-stored and de novo synthesized bioactive compounds. The release and production of mast cell mediators is the result of a coordinated signaling machinery, followed by the FcεRI and FcγR antigen ligation. In this review, we present the latest understanding of FcεRI and FcγR signaling, required for the canonical mast cell activation during allergic responses and anaphylaxis. We then describe the cooperation between the signaling of FcR and other recently characterized membrane-bound receptors (i.e., IL-33R and thymic stromal lymphopoietin receptor) and their role in the chronic settings, where mast cell activation is crucial for the development and the sustainment of chronic diseases, such as asthma or airway inflammation. Finally, we report how the FcR activation could be used as a therapeutic approach to treat allergic and atopic diseases by mast cell inactivation. Understanding the magnitude and the complexity of mast cell signaling is necessary to identify the mechanisms underlying the potential effector and regulatory roles of mast cells in the biology and pathology of those disease settings in which mast cells are activated.Keywords: FcεRI r FcγR r IL-33 r mast cells r TSLP IntroductionMast cells originate in the BM from a lineage-specific multipotent hematopoietic progenitor, circulate as CD34 + precursors until they migrate to tissues and mature into effector cells in the proximity of organs and blood vessels. Mast cells respond to antigenic stimulation through the cross-linking of immunoglobulin E (IgE) bound to high-affinity receptors for IgE (FcεRI) and the activation of the FcγR after IgG binding (reviewed in [1,2]). Upon activation, mast cells release either preformed, granule-stored mediators, such as histamine and proteases, or newly generated mediators, such as eicosanoids, cytokines, and chemokines [3]. Although the basic molecular mechanisms of Ig:Fc activation have been extensively studied in the past 15 years [4][5][6], new molecules regulating the Correspondence: Dr. Barbara Frossi e-mail: barbara.frossi@uniud.it FcR-signaling cascades have recently been characterized, suggesting not only a still vivid interest in the field of mast cell activation and signaling, but also in identifying putative new therapeutic targets for intervention in mast cell dependent disorders. This review will focus on three aspects of mast cell activation/function. First, we give an essential but complete overview of the FcR-mediated activation in mast cells and report on recent advances in IgE-and IgG-mediated signaling. For clarity, we will dissect and analyze the signals derived from each pathway, with particular attention to the newly identified positive or negative molecular players describing -when possible -their implication toward degranulation and cytokine production. Second, we highlight the growing interest aroun...

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“…T he high affinity receptors for IgE (Fc⑀RI) (1)(2)(3)(4) and IgG (Fc␥RI) (1) are both now known to be expressed on human mast cells. Activation of human mast cells through Fc⑀RI is believed to be responsible for allergen-dependent allergic responses in a Th2 environment (5).…”

Section: A Comparison Of Mediators Released or Generated By Ifn-␥-trementioning

confidence: 99%

“…FACS analysis was performed as described (1,16,17). In some experiments, mast cells were preincubated with 1 g/ml of human myeloma IgE (Calbiochem, San Diego, CA) for 16 h. Mast cells were then resuspended in a mixture of PE cyanine 5-conjugated c-kit (CD117), biotin-conjugated goat anti-human IgE ⑀-chain (BioSource International, Camarillo, CA) and FITC-conjugated mouse anti-human Fc␥RI mAb for 30 min at 4°C.…”

Section: Abs and Flow Cytometric Analysismentioning

confidence: 99%

A Comparison of Mediators Released or Generated by IFN-γ-Treated Human Mast Cells Following Aggregation of FcγRI or FcεRI

Okayama

Hagaman

Metcalfe

2001

The Journal of Immunology

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The high affinity receptor for IgG (FcγRI, CD64) is expressed on human mast cells, where it is up-regulated by IFN-γ and, thus, may allow mast cells to be recruited through IgG-dependent mechanisms in IFN-γ-rich tissue inflammation. However, the mediators produced by human mast cells after aggregation of FcγRI are incompletely described, and it is unknown whether these mediators are distinct from those produced after activation of human mast cells via FcεRI. Thus, we investigated the release of histamine and arachidonic acid metabolites and examined the chemokine and cytokine mRNA profiles of IFN-γ-treated cultured human mast cells after FcγRI or FcεRI aggregation. Aggregation of FcγRI resulted in histamine release and PGD2 and LTC4 generation. These responses were qualitatively indistinguishable from responses stimulated via FcεRI. Aggregation of FcεRI or FcγRI led to an induction or accumulation of 22 cytokine and chemokine mRNAs. Among them, seven cytokines (TNF-α, IL-1β, IL-5, IL-6, IL-13, IL-1R antagonist, and GM-CSF) were significantly up-regulated via aggregation of FcγRI compared with FcεRI. TNF-α mRNA data were confirmed by quantitative RT-PCR and ELISA. Furthermore, we confirmed histamine and TNF-α data using IFN-γ-treated purified human lung mast cells. Thus, aggregation of FcγRI on mast cells led to up-regulation and/or release of three important classes of mediators: biogenic amines, lipid mediators, and cytokines. Some cytokines, such as TNF-α, were released and generated to a greater degree after FcγRI aggregation, suggesting that selected biologic responses of mast cells may be preferentially generated through FcγRI in an IFN-γ-rich environment.

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Expression of a Functional High-Affinity IgG Receptor, FcγRI, on Human Mast Cells: Up-Regulation by IFN-γ

Cited by 170 publications

References 49 publications

IgE and IgG antibodies in skin allergy of the horse

IgE and IgG antibodies in skin allergy of the horse

Mast cell activation: A complex interplay of positive and negative signaling pathways

A Comparison of Mediators Released or Generated by IFN-γ-Treated Human Mast Cells Following Aggregation of FcγRI or FcεRI

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