Increased Expression of High Affinity IgE (Fc ɛ RI) Receptor- α Chain mRNA and Protein-bearing Eosinophils in Human Allergen-induced Atopic Asthma (original) (raw)
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Immunology, 2001
We have used in situ hybridization (ISH ) and immunohistochemistry (IHC ) to investigate the kinetics of the expression for FceRI mRNA (a-, b-and c-chains), the a-chain protein product, as well as the phenotype of the mRNA-or protein-positive cells in allergen-induced late-phase skin reactions in atopic subjects. Compared with diluent controls, there were significant increases in the total numbers of mRNA+ cells for the a-, b-and c-chains for FceRI at all time-points (6, 24 and 48 hr) after allergen challenge (P<0·01). By double IHC/ISH significant increases in a-, band c-chain mRNA+ macrophages, eosinophils, mast cells and CD1a+ cells were also observed after allergen challenge (P<0·05). The distribution of FceRI subunit (a-, b-, or c-chain) mRNA+ co-localization was CD68+ macrophages (42-47%), EG2+ eosinophils (33-39%), tryptase+ mast cells (5-11%) and CD1a+ Langerhans' cells (2-4%). Using single IHC, significant increases in the total number of FceRI protein+ cells (P<0·01) were observed 24 and 48 hr after allergen challenge. Double IHC showed that the distribution of FceRI+ cells was tryptase+ mast cells (33%), CD68+ macrophages (36%), EG2+ eosinophils (20%), CD1a+ Langerhans' cells (4%) and unidentified cells (7%), at the 24-hr allergen-challenged sites. These observations suggest that the cutaneous late-phase reaction in man is associated with up-regulation of FceRI on eosinophils, macrophages, mast cells and Langerhans' cells.
Does IgE Bind to and Activate Eosinophils from Patients with Allergy?
The Journal of Immunology
Human eosinophils have been reported to express both the mRNA and protein for the high affinity IgE receptor (FcεRI); it is speculated that this receptor plays a role in eosinophil mediator release in allergic diseases. However, questions still remain. How much of the FcεRI protein is actually expressed on the cell surface of the eosinophil? If they are present, are these IgE receptors associated with effector functions of eosinophils? To address these issues, we studied blood eosinophils from patients with ragweed hay fever. A high level of low affinity IgG receptor (FcγRII, CD32), but no expression of FcεRI, was detectable on the eosinophil surface by standard FACS analysis. However, after in vitro sensitization with biotinylated chimeric IgE (cIgE), cell-bound cIgE was detected by PE-conjugated streptavidin. This cIgE binding was partially inhibited by anti-FcεRI mAb, suggesting that eosinophils do express minimal amounts of FcεRI detectable only by a sensitive method. Indeed, FA...
The Journal of experimental medicine, 1996
The high-affinity receptor for immunoglobulin (Ig) E (Fc epsilon RI) on mast cells and basophils plays a key role in IgE-mediated allergies. Fc epsilon RI is composed of one alpha, one beta, and two gamma chains, which are all required for cell surface expression of Fc epsilon RI, but only the alpha chain is involved in the binding to IgE. Fc epsilon RI-IgE interaction is highly species specific, and rodent Fc epsilon RI does not bind human IgE. 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. 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. 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. Expression of the transgenic Fc epsilon RI...
Journal of Experimental Medicine, 1997
The binding of immunoglobulin E (IgE) to high affinity IgE receptors (FcεRI) expressed on the surface of mast cells primes these cells to secrete, upon subsequent exposure to specific antigen, a panel of proinflammatory mediators, which includes cytokines that can also have immunoregulatory activities. This IgE- and antigen-specific mast cell activation and mediator production is thought to be critical to the pathogenesis of allergic disorders, such as anaphylaxis and asthma, and also contributes to host defense against parasites. We now report that exposure to IgE results in a striking (up to 32-fold) upregulation of surface expression of FcεRI on mouse mast cells in vitro or in vivo. Moreover, baseline levels of FcεRI expression on peritoneal mast cells from genetically IgE-deficient (IgE −/−) mice are dramatically reduced (by ∼83%) compared with those on cells from the corresponding normal mice. In vitro studies indicate that the IgE-dependent upregulation of mouse mast cell FcεR...