Disease relevance of Fcer1a

• Specific inhibition of immunoglobulin E-mediated allergic reaction using antisense Fc epsilon RI alpha oligodeoxynucleotides [1].

High impact information on Fcer1a

• These p161+/Fc epsilon RI- mast cells expressed normal amounts of Fc epsilon RI alpha and beta chain mRNA, but extremely low levels of Fc epsilon RI gamma chain mRNA [2].
• As a first step in developing an in vivo model that more closely mimics the IgE-mediated responses in man, we used a combination of transgenic and embryonic stem cell technology to generate a mouse line in which the murine Fc epsilon RI alpha-chain has been replaced with its human homologue [3].
• There was a slight transient increase at 4 h in the level of proteoglycan peptide core mRNA, but no increase in the levels of those highly expressed mRNA that encode actin, Fc epsilon RI alpha, carboxypeptidase A, and serine protease [4].
• In addition, we show that a single gene for FC epsilon RI gamma is found at the distal end of mouse chromosome 1, clustered in a region where Fc epsilon RI alpha has also been linked to Fc gamma RII [5].
• Analysis of the segregation of restriction fragment length polymorphism in crosses of inbred mice now establish that the structural genes encoding both Fc epsilon RI alpha and Fc gamma 2b/gamma 1R are indeed discrete genes and are linked at the distal end of mouse chromosome 1 [6].

Biological context of Fcer1a

• The close association of the genes for Fc epsilon RI alpha, FC gamma RII, and their shared gamma subunits raises interesting implications regarding coordinate regulation of gene expression [5].
• These results indicate that 44.7b binds to an epitope on the IgE molecule which is within the binding site of the mast cell IgE Fc receptor (FcERI) [7].

Anatomical context of Fcer1a

• Recently isolated cDNA clones for the high affinity Fc epsilon receptors on mast cells and basophils (Fc epsilon RI alpha) and Fc gamma receptors on macrophages and lymphocytes (Fc gamma 2b/gamma 1R) are homologous members of the Ig supergene family [6].
• Further studies with the mouse anti-human Fc epsilon RI alpha antibody 29C6 showed that mast cells and basophils were similarly sensitive to IgG-mediated direct cross-linking of Fc epsilon RI, with 0.01-1.0 micrograms/ml 29C6 evoking histamine release in each case [8].

Regulatory relationships of Fcer1a

• Synthetic antisense Fc epsilon RI alpha ODN dose-dependently inhibited passive cutaneous anaphylaxis and histamine release from the mouse peritoneal mast cells (MPMC) activated by anti-dinitrophenyl (DNP) IgE [1].

Other interactions of Fcer1a

• Northern blot analysis showed that the mast cells treated with antisense Fc epsilon RI alpha ODN exhibited no detectable levels of L-histidine decarboxylase mRNA after anti-DNP IgE stimulation, whereas the cells treated with sense Fc epsilon RI alpha ODN possessed significant amounts of this mRNA [1].
• A synthetic cyclized 13-amino acid peptide was previously designed from the modeled C-C' loop region of the Fc epsilon RI alpha-chain and was found to act as a competitive inhibitor of IgE-Fc epsilon RI alpha binding [9].

Analytical, diagnostic and therapeutic context of Fcer1a

• Using the polymerase chain reaction procedure, we have extended these findings to show that one Fc epsilon RI-alpha mRNA variant, characterized by a 163-bp deletion within the coding sequence, exists in normal rat connective tissue mast cells as well as in both transformed and non transformed murine mast cell lines [10].
• The humanization of CRA2 might be an important step in the development of immunotherapy to manipulate the IgE network in which mast cells, basophils, and various types of Fc epsilon RI alpha expressing cells are involved [11].
• The activities of the recombinant antibodies to bind Fc epsilon RI alpha and inhibit IgE binding to Fc epsilon RI alpha were analyzed by flow cytometry and ELISA [11].

References