IgE Enhances Mouse Mast Cell FcεRI Expression In Vitro and In Vivo: Evidence for a Novel Amplification Mechanism in IgE-dependent Reactions
Autor: | Chris S. Lantz, Stephen J. Galli, Masao Yamaguchi, Ichiro Miyajima, Hans C. Oettgen, Tony Fleming, Jean-Pierre Kinet, Ildy M. Katona |
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Rok vydání: | 1997 |
Předmět: |
Immunology
Bone Marrow Cells Immunoglobulin E Article Proinflammatory cytokine Mice 03 medical and health sciences 0302 clinical medicine Downregulation and upregulation Antigen Bone Marrow medicine Animals Immunology and Allergy Secretion Mast Cells Cycloheximide Receptor Peritoneal Cavity Cells Cultured 030304 developmental biology 0303 health sciences biology Receptors IgE Articles Mast cell In vitro Up-Regulation 3. Good health medicine.anatomical_structure biology.protein 030215 immunology |
Zdroj: | The Journal of Experimental Medicine |
ISSN: | 1540-9538 0022-1007 |
DOI: | 10.1084/jem.185.4.663 |
Popis: | The binding of immunoglobulin E (IgE) to high affinity IgE receptors (Fc(epsilon)RI) expressed on the surface of mast cells primes these cells to secrete, upon subsequent exposure to specific antigen, a panel of proinflammatory mediators, which includes cytokines that can also have immunoregulatory activities. This IgE- and antigen-specific mast cell activation and mediator production is thought to be critical to the pathogenesis of allergic disorders, such as anaphylaxis and asthma, and also contributes to host defense against parasites. We now report that exposure to IgE results in a striking (up to 32-fold) upregulation of surface expression of Fc(epsilon)RI on mouse mast cells in vitro or in vivo. Moreover, baseline levels of Fc(epsilon)RI expression on peritoneal mast cells from genetically IgE-deficient (IgE -/-) mice are dramatically reduced (by approximately 83%) compared with those on cells from the corresponding normal mice. In vitro studies indicate that the IgE-dependent upregulation of mouse mast cell Fc(epsilon)RI expression has two components: an early cycloheximide-insensitive phase, followed by a later and more sustained component that is highly sensitive to inhibition by cycloheximide. In turn, IgE-dependent upregulation of Fc(epsilon)RI expression significantly enhances the ability of mouse mast cells to release serotonin, interleukin-6 (IL-6), and IL-4 in response to challenge with IgE and specific antigen. The demonstration that IgE-dependent enhancement of mast cell Fc(epsilon)RI expression permits mast cells to respond to antigen challenge with increased production of proinflammatory and immunoregulatory mediators provides new insights into both the pathogenesis of allergic diseases and the regulation of protective host responses to parasites. |
Databáze: | OpenAIRE |
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