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Vol. 154, No. 1, 2011
Issue release date: December 2010
Section title: Original Paper
Int Arch Allergy Immunol 2011;154:15–24
(DOI:10.1159/000319204)

IgE-Dependent and IgE-Independent Stimulation of Human Basophils Increases the Presence of Immature FcεRIα by Reversing Degradative Pathways

Zaidi A.K. · MacGlashan, Jr. D.
Johns Hopkins Asthma and Allergy Center, Baltimore, Md., USA

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Article / Publication Details

First-Page Preview
Abstract of Original Paper

Received: 9/10/2009
Accepted: 1/20/2010
Published online: 7/24/2010

Number of Print Pages: 10
Number of Figures: 6
Number of Tables: 0

ISSN: 1018-2438 (Print)
eISSN: 1423-0097 (Online)

For additional information: http://www.karger.com/IAA

Abstract

Background: Expression of the high-affinity IgE receptor, FcεRI, on mast cells and basophils has previously been shown to be sensitive to the presence of IgE or cytokines. The current study examined whether stimulation of human basophils resulted in a change in the expression of FcεRI. Methods: Changes in the well-expressed immature intracellular form of the receptor, FcεRIα (p46), were examined by quantitative PCR, Western blot and the pulse-chase method. Results: Both IgE-dependent (anti-IgE antibody) and IgE-independent stimulation [formyl-methionyl-leucyl-phenylalanine (FMLP) and C5a] led to increased accumulation of p46. The p46 form of FcεRIα increased 1.52 ± 0.09-, 2.58 ± 0.09- and 1.47 ± 0.07-fold following stimulation with anti-IgE, FMLP and C5a, respectively. There were no changes in the steady-state levels of mRNA for FcεRIα. The kinetics of the increase in p46 was slow following stimulation with anti-IgE antibody, with the earliest increases observed after 8 h. The p46 form was degraded in a bafilomycin A (lysosomal inhibitor)-sensitive process. There was no synergy between treatment with bafilomycin A and anti-IgE or FMLP stimulation, suggesting that the 2 methods of enhancement operate on the same pathway. Pulse-chase studies corroborated this conclusion. In contrast, IL-3 and bafilomycin A synergistically increased p46, suggesting that IL-3 increased synthesis of FcεRIα. Conclusions: Taken together, these results suggest that secretagogue stimulation results in an increase in p46 due to reversal of degradative pathways rather than increased synthesis of FcεRIα. Nevertheless, a decrease in the degradation of FcεRIα at an intermediate step in its processing by non-FcεRI-dependent stimulation may still influence expression of this important receptor.


Article / Publication Details

First-Page Preview
Abstract of Original Paper

Received: 9/10/2009
Accepted: 1/20/2010
Published online: 7/24/2010

Number of Print Pages: 10
Number of Figures: 6
Number of Tables: 0

ISSN: 1018-2438 (Print)
eISSN: 1423-0097 (Online)

For additional information: http://www.karger.com/IAA


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Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
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