Coding single nucleotide polymorphism in the high‐affinity immunoglobulin E receptor b chain (Fc"RI‐b) gene is associated with immunoglobulin E receptor‐mediated histamine release from basophils

Kim, Y. K.; Oh, Sun Young; Oh, Hyeon-Jeong; Chun, Susan; Cho, Sang Heon; Koh, Young Yull; Min, Kyung Up; Kim, Y. Y.

doi:10.1046/j.1365-2222.2002.01295.x

Cited by 20 publications

(22 citation statements)

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“…Aggregation of Fc⑀RI by the interaction of bound IgE with multivalent antigens induces the release of histamine, leukotrienes, and inflammatory cytokines, resulting in the recruitment and activation of circulating leukocytes leading to allergic inflammation (2). Polymorphisms in the Fc⑀RI␤ have been linked to atopy, asthma, and allergy (3)(4)(5). However, studies on the role of these polymorphisms in Fc⑀RI expression and function have not yielded an understanding of their effects on mast cell physiology (6,7).…”

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confidence: 99%

The FcϵRIβ Immunoreceptor Tyrosine-based Activation Motif Exerts Inhibitory Control on MAPK and IκB Kinase Phosphorylation and Mast Cell Cytokine Production

Furumoto

Nunomura

Terada

et al. 2004

Journal of Biological Chemistry

125

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The high affinity IgE Fc receptor (Fc⑀RI) ␤ chain functions as a signal amplifier and has been linked to atopy, asthma, and allergy. Herein, we report on a previously unrecognized negative regulatory role for the nonconventional ␤ chain immunoreceptor tyrosine-based activation motif that contains three tyrosine residues (YX 5 YX 3 Y). Degranulation and leukotriene production was found to be impaired in cells expressing the mutated Fc⑀RI␤ immunoreceptor tyrosine-based activation motifs FYY, YYF, FYF, and FFF. In contrast, cytokine synthesis and secretion were enhanced in the YFY and FFF mutants. Fc⑀RI phosphorylation and Lyn kinase co-immunoprecipitation was intact in the YFY mutant but was lost in the FYF and FFF mutants. The phosphorylation of Syk, LAT, phospholipase ␥1/2, and Srchomology 2 domain-containing protein phosphatase 2 was intact, whereas the phosphorylation of SHIP-1 was significantly reduced in the YFY mutant cells. The FYF and FFF mutants were defective in phosphorylating all of these molecules. In contrast, the phosphorylation of ERK, p38 MAPK, IB kinase ␤ (IKK␤), and nuclear NFB activity was enhanced in the YFY and FFF mutants. These findings show that the Fc⑀RI␤ functions to both selectively amplify (degranulation and leukotriene secretion) and dampen (lymphokine) mast cell effector responses.The Fc⑀RI 1 in mast cells and basophils is a tetrameric structure consisting of three distinct polypeptides including the IgE-binding ␣ chain, the tetraspanning ␤ chain, and the disulfide-linked ␥ homodimer (1). Aggregation of Fc⑀RI by the interaction of bound IgE with multivalent antigens induces the release of histamine, leukotrienes, and inflammatory cytokines, resulting in the recruitment and activation of circulating leukocytes leading to allergic inflammation (2). Polymorphisms in the Fc⑀RI␤ have been linked to atopy, asthma, and allergy (3-5). However, studies on the role of these polymorphisms in Fc⑀RI expression and function have not yielded an understanding of their effects on mast cell physiology (6, 7). Nonetheless, it is clear that the Fc⑀RI␤ functions as a signal amplifier in mast cells and is important for augmenting the allergic reactions (8 -10). In humans, it has been demonstrated that the ␥ homodimer can act as an autonomous signaling molecule in various cell types, whereas the ␤ subunit amplifies early activation signals by 5-7-fold through Fc⑀RI (reviewed in Ref. 1). Moreover, the ␤ chain also enhances cell-surface expression of Fc⑀RI (11), providing increased sensitivity in an allergic response.The ␤-and ␥-chains contain ITAMs, a conserved feature of many antigen receptors that imparts signaling competence. The ITAM consensus sequence is (D/E)XXYXXLX 7-11 -YXXL(L/ I), where the tyrosine residues are phosphoacceptor sites for the action of receptor-associated protein tyrosine kinases (reviewed in Ref. 1). Phospho-ITAMs provide a docking site for cytoplasmic proteins that contain the Src-homology 2 (SH2) domain. Some of these function to couple receptors to macromolecular signaling comp...

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confidence: 99%

The FcϵRIβ Immunoreceptor Tyrosine-based Activation Motif Exerts Inhibitory Control on MAPK and IκB Kinase Phosphorylation and Mast Cell Cytokine Production

Furumoto

Nunomura

Terada

et al. 2004

Journal of Biological Chemistry

125

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“…While the genes for the alpha and gamma subunits are both located on human and mouse chromosome 1 (18), the beta gene is located on 11q13 and spans about 10 kb and contains 7 exons (19). Although polymorphisms of the FCER1B gene has been reported to be associated with atopy, total serum IgE level, bronchial hyperresponsiveness, asthma, and the basophilic histamine-releasing activity of asthmatic patients (8-11, 20), no previous study has been made of the association between FCER1B gene polymorphisms and urticaria/angioedema. This study, therefore, is the first to investigate whether no significant association is found between the FCER1B gene polymorphism with the AIU phenotype in a Korean population.…”

Section: Discussionmentioning

confidence: 99%

Polymorphisms of High-Affinity IgE Receptor and Histamine-Related Genes in Patients with ASA-Induced Urticaria/Angioedema

et al. 2005

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The pathogenic mechanism of ASA-induced urticaria/angioedema (AIU) is still poorly understood, but it has been known that histamine releasing by cutaneous mast cell activation is considered to be an important role. Considering the importance of histamine in AIU, we speculated that a genetic abnormality of histamine-related genes such as a high-affinity IgE receptor, a metabolic enzyme of histamines and histamine receptors, may be involved in the development of AIU. Enrolled in the study were 110 patients with AIU, 53 patients without ASA hypersensitivity who had various drug allergies presenting as exanthematous skin symptoms, and 99 normal healthy controls (NC). Eleven single nucleotide polymorphisms (SNPs) of the β chain of the high-affinity IgE receptor (FCER1B) and three histamine-related genes-histamine N-methyltransferase (HNMT), histamine H1 receptor (HRH1), histamine H2 receptor (HRH2)-were screened using the SNP-IT assay based on a single base extension method. No significant differences were observed in allele and genotype frequencies, and haplotype frequencies of all the SNPs of FCER1B, HNMT, HRH1, and HRH2 among the three groups (p>0.05, respectively). These results suggest that the polymorphisms of FCER1B and the three histamine-related genes may not contribute to the development of AIU phenotype in the Korean population.

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“…Genetic studies revealed that a locus in the long arm (q) of chromosome 11 at bands 12-13 (11q12-13), which contains the FcεRIβ gene, is linked with allergy [10,14]. Additional analysis revealed the identified polymorphisms as associated with atopy, asthma, allergic rhinitis, bronchial hyperesponsiveness, atopic dermatitis, total serum IgE levels, and histamine release from basophils in various populations [9,[11][12][13]. The described single nucleotide polymorphisms (SNPs) in In contrast, the YFY mutant showed enhanced cytokine synthesis and secretion of IL-6, IL-13, and TNF-α (Fig.…”

Section: Fcεriβ Polymorphisms and Link To Allergic Diseasementioning

confidence: 99%

“…Kinet and colleagues [7,8], demonstrated that the β subunit serves a key role in amplifying the intracellular signaling that is important for mast cell release of a variety of preformed allergic mediators. This key role in amplifying responses, and thus controlling the sensitivity of a mast cell, has led to the hypothesis that polymorphisms in the β subunit shown be linked to atopy, allergy, and asthma [9][10][11][12][13][14], might affect the signaling ability of the β subunit and thus FcεRI. However, several studies have explored this possibility by reconstituting cellular expression of the polymorphic β subunit without achieving any measurable changes in cellular function [15,16].…”

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New Insights on the Allergy-Linked β Subunit of the High Affinity IgE Receptor: Mechanisms and Clinical Implications

Furumoto¹,

Takasugi²,

Rivera³

2005

CIR

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The high affinity IgE Fc receptor (FcεRI) on mast cells and basophils has a central role in allergy and asthma. The β subunit of this multimeric receptor is a membrane tetra-spanning protein that encodes a nonconventional immunoreceptor tyrosine-based activation motif (ITAM) that imparts it signaling competence. This subunit was shown to amplify FcεRI signaling causing increased cellular responses such as degranulation. Polymorphisms of the β subunit have been linked to atopy, asthma, and allergy. Although considerable effort has been made to understand the functional consequence(s) of expressing these polymorphisms, the outcome has not been revealing. Recent studies show a link between β subunit polymorphisms, β gene transcription, and increased FcεRI expression. Additionally, a newly described function for the β subunit suggests an important role in downregulating cytokine production. Among the molecules whose response is dampened by FcεRIβ is NFκB, a central regulator of inflammation. Collectively, these studies suggest that the β subunit is important in controlling the sensitivity and extent of an elicited response upon mast cell or basophil activation. Thus the findings, described herein, provide new insights on the mechanistic link between the FcεRIβ and allergic disease.

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Coding single nucleotide polymorphism in the high‐affinity immunoglobulin E receptor b chain (Fc"RI‐b) gene is associated with immunoglobulin E receptor‐mediated histamine release from basophils

Abstract: This study supports a role for the FcepsilonRI-beta gene in the expression of high affinity IgE receptor-mediated histamine release from basophils.

Cited by 20 publications

References 20 publications

The FcϵRIβ Immunoreceptor Tyrosine-based Activation Motif Exerts Inhibitory Control on MAPK and IκB Kinase Phosphorylation and Mast Cell Cytokine Production

The FcϵRIβ Immunoreceptor Tyrosine-based Activation Motif Exerts Inhibitory Control on MAPK and IκB Kinase Phosphorylation and Mast Cell Cytokine Production

Polymorphisms of High-Affinity IgE Receptor and Histamine-Related Genes in Patients with ASA-Induced Urticaria/Angioedema

New Insights on the Allergy-Linked β Subunit of the High Affinity IgE Receptor: Mechanisms and Clinical Implications

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Coding single nucleotide polymorphism in the high‐affinity immunoglobulin E receptor b chain (Fc"RI‐b) gene is associated with immunoglobulin E receptor‐mediated histamine release from basophils

Abstract: This study supports a role for the FcepsilonRI-beta gene in the expression of high affinity IgE receptor-mediated histamine release from basophils.

Cited by 20 publications

References 20 publications

The FcϵRIβ Immunoreceptor Tyrosine-based Activation Motif Exerts Inhibitory Control on MAPK and IκB Kinase Phosphorylation and Mast Cell Cytokine Production

The FcϵRIβ Immunoreceptor Tyrosine-based Activation Motif Exerts Inhibitory Control on MAPK and IκB Kinase Phosphorylation and Mast Cell Cytokine Production

Polymorphisms of High-Affinity IgE Receptor and Histamine-Related Genes in Patients with ASA-Induced Urticaria/Angioedema

New Insights on the Allergy-Linked &#946; Subunit of the High Affinity IgE Receptor: Mechanisms and Clinical Implications

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New Insights on the Allergy-Linked β Subunit of the High Affinity IgE Receptor: Mechanisms and Clinical Implications