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RI
up-regulation by IgE in human basophils
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
RI
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
RI
, 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
RI
was coordinated with
up-regulation of other components of the IgE-signaling pathway. The
results indicated up-regulation of Fc
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
RI
immunoglobulin E basophils
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