Disease relevance of FCER1A

• Novel exon 2A of the high-affinity receptor for the IgE alpha-chain gene (FCER1A) and autoimmunity in patients with asthma or urticaria [1].
• To obtain a "humanized" animal model that responds to human IgE in allergic reactions, transgenic mice expressing the human Fc epsilon RI alpha chain were generated [2].
• We conclude that eosinophils possess a sizable intracellular pool of Fc epsilon RI alpha that is available for release, with undetectable surface levels in a variety of subjects, including those with eosinophilia and elevated serum IgE [3].
• In this study, the randomized pentapeptides were introduced between Glu(132) and Ile(138) of Fc epsilon RI alpha D2 and displayed on a filamentous phage [4].

High impact information on FCER1A

• Cell surface expression of the human Fc epsilon RI alpha chain was indicated by the specific binding of human IgE to mast cells from transgenic mice in flow cytometric analyses [2].
• The human Fc epsilon RI alpha chain gene with a 1.3-kb promoter region as a transgene was found to be sufficient for mast cell-specific transcription [2].
• Specific transcripts for Fc epsilon RI alpha and Fc epsilon RI gamma were detected in LC and correspond to those of human basophils and of the human basophil cell line KU812 [5].
• In Fc epsilon RI(pos) DCs expressing Fc epsilon RI gamma, an additional mature form of Fc epsilon RI alpha exhibiting complex glycosylation colocalizes with Fc epsilon RI gamma in the Golgi compartment [6].
• We show that in all donors intracellular alpha chain of the Fc epsilon RI (Fc epsilon RI alpha) accumulates during DC differentiation from monocytes [6].

Biological context of FCER1A

• By mapping the 5' end of Fc epsilon RI alpha transcripts we found three major transcription initiation sites 24, 27, and 29 bp upstream of the ATG translation initiation codon [7].
• As with the previously characterized rat and mouse genes, human Fc epsilon RI alpha consists of five exons and four introns, and spans 5889 bp of genomic DNA [7].
• To localize the high affinity IgE binding site within the Fc epsilon RI alpha subunit, we generated a series of chimeric receptor constructs where one of the two immunoglobulin-like domains was either deleted or substituted with those from the human Fc gamma RIIIA alpha or the rat Fc epsilon RI alpha subunit [8].
• Functional characterization of the signal transduction events mediated by Fc epsilon RI alpha and gamma chimeric receptors [9].
• These results suggest that the suppression of Fc epsilon RI expression by PPARs may be due to the down-regulation of Fc epsilon RI alpha or gamma mRNA [10].

Anatomical context of FCER1A

• In Fc epsilon RI(neg) DCs lacking Fc epsilon RI gamma, immature and core glycosylated Fc epsilon RI alpha accumulates in the endoplasmic reticulum [6].
• This receptor occurs on the surface of these cells as a multimeric structure containing Fc epsilon RI alpha- and Fc epsilon RI gamma-chains but, unlike its counterpart on basophils, lacking Fc epsilon RI beta [11].
• Peripheral blood dendritic cells express Fc epsilon RI as a complex composed of Fc epsilon RI alpha- and Fc epsilon RI gamma-chains and can use this receptor for IgE-mediated allergen presentation [11].
• RESULTS: Cytoplasmic Fc epsilon RI alpha chain was found in Langerhans' cells from all donors, irrespective of atopic status [12].
• Comparable amounts of Fc epsilon RI alpha and Fc epsilon RI gamma mRNA molecules were measured in basophils and tissue-derived mast cells, lesser amounts were detected in KU812 cells, and almost none was detected in HMC-1 cells [13].

Associations of FCER1A with chemical compounds

• Both proteins blocked the release of histamine from RBL cells expressing human Fc epsilon RI alpha in a dose-dependent manner [14].
• Levels of tryptase, chymase, and Fc epsilon RI alpha messenger RNA in human skin are unchanged after IgE-dependent stimulation of cutaneous mast cells in vivo [15].
• In steroid-treated AAPs Fc epsilon RI alpha-chain expression returned to the level found in BMs from NASs [16].
• We find that only N371 and N394 are glycosylated, and that the residues surrounding the glycosylation site at N394 are required for Fc epsilon RI alpha binding activity [17].
• Depending on the inducing factor, surface expression of the Fc epsilon RI alpha-chain was increased from 20% to 35-50% of the cells and mRNA levels for tryptase were increased in serum-free medium and after DMSO treatment [18].

Physical interactions of FCER1A

• The large surface area of IgE and Fc epsilon RI alpha that is implicated in complex formation from previous mutagenesis studies on the two proteins may account in part for the magnitude of Delta Cp degrees [19].

Regulatory relationships of FCER1A

• IL-4 also enhanced the expression of Fc epsilon RI alpha, a high affinity IgE receptor, on the cell surface [20].
• Reverse transcription polymerase chain reaction showed that CD14+ alveolar macrophages expressed Fc epsilon RI alpha, beta and gamma chain mRNA [21].

Other interactions of FCER1A

• Within this contig a 1.1-Mb BAC and PAC core segment joining CD1D to FCER1A was fully sequenced and thoroughly analyzed [22].
• Further experiments revealed that these Fc epsilon RI alpha gamma-expressing cells closely resemble peripheral blood DC by immunophenotype (HLA-DRhigh, HLA-DQhhigh; CD4+, CD11a+, CD32+, CD33+, B7/2 (CD86)+; CD11blow, CD14low, CD40low, CD54low, CD64low) and cell morphology [11].
• CD54 and Fc epsilon RI alpha also were expressed constitutively [23].
• Induction of Fc epsilon RI alpha mRNA and protein synthesis by interleukin 4 in CD34+ cells-derived CD1a+ dendritic cells [24].
• CONCLUSION: Two different pathways by which Fc epsilon RI alpha-chain expression was modulated in BMs were identified: (1) the enhancing effect of IL-4 and IL-13 and (2) the inhibitory effect of GCs [16].

Analytical, diagnostic and therapeutic context of FCER1A

• METHODS: Intact epidermal sheets from skin suction blisters, immunofluorescently stained with Langerhans' cell markers and anti-Fc epsilon RI alpha (mAbs 15E5 and 22E7) or anti-IgE, were examined by means of confocal microscopy [12].
• The transgenic human Fc epsilon RI alpha chain was complexed with the mouse beta and gamma chains in immunoprecipitation studies [2].
• Titrations, however, reveal that the IgE-Fc forms an equimolar complex with a soluble fragment of the Fc epsilon RI alpha chain (sFc epsilon RI alpha), and the molecular weight of the complex, as determined by sedimentation equilibrium, confirms this stoichiometry [25].
• Peripheral blood and bronchoalveolar lavage (BAL) PMNs from asthmatic subjects also express intracellular Fc epsilon RI alpha and beta chain immunoreactivity [26].
• Immunoprecipitation and Western blotting demonstrated the release of Fc epsilon RI alpha into the supernatant of cultured eosinophils, peaking at approximately 48 h [3].

References