Antigen-induced reduction in mast cell and basophil functional responses due to reduced Syk protein levels
- UNCG Author/Contributor (non-UNCG co-authors, if there are any, appear on document)
- Christopher Kepley, Associate Professor (Creator)
- Institution
- The University of North Carolina at Greensboro (UNCG )
- Web Site: http://library.uncg.edu/
Abstract: Background: The high-affinity IgE receptor, FceRI, is unresponsive on mast cells and basophils from people in several populations through an unknown mechanism. Similarly, FceRI-positive basophils from ‘nonreleasers’ are IgE-unresponsive and are deficient in the tyrosine kinase Syk. Objective: To test the hypothesis that cross-linking FceRI on mast cells and basophils leads to FceRI nonresponsiveness through reduction in Syk protein levels. Methods: Human mast cells and basophils were used to determine if FceRI hyporesponsiveness correlated with reduced Syk levels. Results: It is shown that suboptimal antigen challenge, that did not lead to significant mediator release, induced nonresponsiveness and correlated with reduced Syk. Other IgE-associated signaling molecules were unaffected by the same treatment. The ability of IgE-unresponsive mast cells to regain FceRI responsiveness is paralleled by increased cellular Syk levels in vitro. The reduction of Syk levels with suboptimal antigen concentrations was calcium independent and mediated through a proteasome-dependent mechanism. Conclusion: These findings confirm and extend our knowledge about a novel regulatory mechanism for maintaining FceRI in a quiescent state. This mechanism may also explain why low concentrations of allergen given to patients during allergen immunotherapy induce FceRI nonresponsiveness and therapeutic benefit without inducing systemic anaphylaxis.
Antigen-induced reduction in mast cell and basophil functional responses due to reduced Syk protein levels
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Created on 8/13/2019
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Additional Information
- Publication
- International Archives of Allergy and Immunology 2005; 138:29-39
- Language: English
- Date: 2005
- Keywords
- Mast cells/basophil, IgE, FceRI, Signal transduction, Desensitization