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(Journal of Leukocyte Biology. 2000;68:479-486.)
© 2000 by Society for Leukocyte Biology

Functional consequences of Fc{varepsilon}RI{alpha} up-regulation by IgE in human basophils

Donald MacGlashan, Jr and John T. Schroeder

Johns Hopkins Asthma and Allergy Center, Baltimore, Maryland

Correspondence: Donald MacGlashan, Jr., Johns Hopkins Asthma and Allergy Center, 5501 Hopkins Bayview Circle, Baltimore, MD 21224. E-mail: dmacglas{at}welch.jhu.edu

These studies examine the functional changes that occur after up-regulation of Fc{varepsilon}RI{alpha} 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-Fc{varepsilon}RI{alpha}, 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 Fc{varepsilon}RI{alpha} was coordinated with up-regulation of other components of the IgE-signaling pathway. The results indicated up-regulation of Fc{varepsilon}RI 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.

Key Words: Fc{varepsilon}RI{alpha} • immunoglobulin E • basophils




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