Induction of Basophil Desensitization in Physiological Medium: Enhancement after IgE-Dependent Upregulation of Surface IgE Binding on BasophilsKomiya A. · Hirai K. · Iikura M. · Nagase H. · Yamada H. · Miyamasu M. · Ohta K. · Morita Y. · Ra C. · Yamamoto K. · Yamaguchi M.
Departments of aAllergy and Rheumatology, bBioregulatory Function and cRespiratory Medicine, University of Tokyo Graduate School of Medicine, dDepartment of Medicine, Teikyo University School of Medicine and eAllergy and Atopy Research Center, Juntendo University School of Medicine, Tokyo, Japan
Background: Although the ability of basophils to release mediators, called releasability, may be an important aspect which influences the proinflammatory role of these cells, clinical approaches aiming at the depletion of the releasability have not been established. We examined whether the desensitization procedure in Ca2+-containing physiological conditions can make basophils completely unresponsive to IgE-mediated stimulation, and whether basophil desensitization is affected by the surface IgE levels. Methods: Human peripheral blood basophils were cultured with low concentrations of anti-IgE antibody or recombinant mite allergen. Following culture, cells were stimulated and their histamine release was measured. Results: Culturing with mite allergen or anti-IgE antibody below threshold concentrations induced potent desensitization in basophils. The desensitizing effect of anti-IgE was dose- and time-dependent; IgE-dependent releasability was completely suppressed when basophils were incubated with a near-threshold concentration of anti-IgE for ≧4 h. In the continuous presence of subthreshold doses of anti-IgE, basophils remained desensitized even after 3 days. Basophils which had undergone an increase in surface IgE levels after 24-hour culture with IgE demonstrated enhanced desensitization. Conclusions: Near-threshold stimulation in physiological medium can affect basophils, thereby inducing complete and sustained deprivation of releasability without triggering degranulation. Basophil desensitization is regulated by their surface IgE levels. Induction of full desensitization may represent a potentially important therapeutic strategy for IgE-mediated allergic diseases in which basophils play pathogenic roles.
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