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Table of Contents
Vol. 124, No. 1-3, 2001
Issue release date: January – March
Section title: Mast Cells
Int Arch Allergy Immunol 2001;124:137–141
(DOI:10.1159/000053692)

A Perspective: Regulation of IgE Receptor-Mediated Mast Cell Responses by a LAT-Organized Plasma Membrane-Localized Signaling Complex

Rivera J. · Arudchandran R. · Gonzalez-Espinosa C. · Manetz T.S. · Xirasagar S.
Section on Chemical Immunology, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Md., USA

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Article / Publication Details

First-Page Preview
Abstract of Mast Cells

Published online: January 24, 2012
Issue release date: January – March

Number of Print Pages: 5
Number of Figures: 1
Number of Tables: 0

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

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

Abstract

Background: To understand how the high-affinity IgE receptor (FcΕRI) communicates with downstream effectors, we focused on exploring the functional importance of the FcΕRI-mediated formation and localization of a signaling complex that contains the hematopoietic cell-specific scaffolding protein linker for activation of T cells (LAT) and the guanine nucleotide exchange factor Vav1. Methods: Using the mast cell line RBL-2H3, we explored the localization of these proteins by confocal microscopy and cell fractionation. Additionally, the mechanism of function and the importance of LAT and Vav1 to mast cells was studied in genetically disrupted mice and in mast cells derived from their bone marrow. Results: We found that LAT, Vav1 and the adapter molecule SLP-76 associated in detergent-resistant microdomains (lipid rafts) found in the plasma membrane upon FcΕRI stimulation. In the absence of LAT, mast cells showed a remarkable loss of the secretory response and reduced cytokine responses. Vav1 deficiency also affected secretion, although not to the extent of LAT deficiency, and inhibited IL-2 and IFN-γ production. LAT- and Vav1-deficient mice showed reduced blood histamine levels after a systemic anaphylaxis challenge as compared to their normal counterparts. Conclusions: The results demonstrate that LAT is a central mediator in IgE receptor signaling by regulating multiple signaling pathways that affect mast cell degranulation and cytokine production. Vav1, a component of this LAT-containing signaling complex, regulates a specific subset of these responses.

© 2001 S. Karger AG, Basel


Article / Publication Details

First-Page Preview
Abstract of Mast Cells

Published online: January 24, 2012
Issue release date: January – March

Number of Print Pages: 5
Number of Figures: 1
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 government 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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