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Published on: November 1, 2014
Functional consequences of FcepsilonRIalpha up-regulation by IgE in human basophils
1Johns Hopkins Asthma and Allergy Center, Baltimore, Maryland 21224, USA. dmacglas@welch.jhu.edu
Insights
Human basophils showed increased responsiveness to antigen challenges after immunoglobulin E (IgE) up-regulation. However, this functional change was modulated, as not all signaling pathway components were balanced.
Area of Science:
- Immunology
- Cell Biology
Background:
- Human basophils express the high-affinity IgE receptor (FcεRIα).
- IgE binding to FcεRIα can lead to basophil activation and mediator release.
Purpose of the Study:
- To investigate functional changes in human basophils following FcεRIα up-regulation induced by IgE.
- To determine if FcεRIα up-regulation is coordinated with other components of the IgE signaling pathway.
Main Methods:
- Human basophils were cultured with or without IgE antibodies for one week.
- Cells were challenged with anti-IgE, anti-FcεRIα, or specific antigen to measure histamine and IL-4 secretion.
- Basophil sensitivity was assessed to evaluate signaling pathway component coordination.
Main Results:
- FcεRIα expression increased approximately 4-fold, but responses to anti-IgE or anti-receptor antibodies did not significantly change.
- Basophils exhibited enhanced responsiveness to antigenic challenge, particularly at suboptimal antigen concentrations.
- Increased antigen potency and histamine release were observed with higher cell surface IgE density, with similar trends for IL-4 secretion.
- FcεRIα up-regulation was not always accompanied by coordinated changes in other signaling pathway components, affecting basophil sensitivity.
Conclusions:
- Up-regulation of FcεRIα in human basophils leads to functional changes, including increased responsiveness to antigen.
- The magnitude of functional up-regulation is modulated due to imbalanced up-regulation of signaling pathway components.
- This suggests that coordinated regulation of the entire IgE signaling pathway is crucial for maintaining basophil sensitivity.
Abstract:
These studies examine the functional changes that occur after up-regulation of FcepsilonRIalpha by immunoglobulin E (IgE) for human basophils. Basophils were cultured with and without IgE antibody (PS myeloma IgE or anti-gp120-specific IgE) for 1 week and challenged with anti-IgE, anti-FcepsilonRIalpha, or antigen for histamine and IL-4 secretion. There were no statistically significant changes in their response to anti-IgE or anti-receptor antibodies, as compared with controls incubated for the same period, whereas receptor expression increased an average of 4-fold. There was increased responsiveness to antigenic challenge, most notably at suboptimal concentrations of antigen (gp120 peptide-ovalbumin conjugate). For a 6-fold difference in cell surface density of gp120-specific IgE, there was a 2.2-fold change in antigen potency or 3-fold increases in histamine release at lower antigen concentrations. Similar results were found for secretion of IL-4. Basophil sensitivity, which is a measure of the density of antigen-specific IgE required for 50% of maximal secretion, was used to determine whether up-regulation of FcepsilonRIalpha was coordinated with up-regulation of other components of the IgE-signaling pathway. The results indicated up-regulation of FcepsilonRI is not always accompanied by changes that allow sensitivity to be maintained. These results indicate that functional up-regulation does occur but that its magnitude may be modulated because not all components of the signaling pathway are up-regulated in a balanced manner.
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