IgE Enhances Mouse Mast Cell FcεRI Expression In Vitro and In Vivo: Evidence for a Novel Amplification Mechanism in IgE-dependent Reactions

Abstract

The binding of immunoglobulin E (IgE) to high affinity IgE receptors (FcεRI) 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 FcεRI on mouse mast cells in vitro or in vivo. Moreover, baseline levels of FcεRI expression on peritoneal mast cells from genetically IgE-deficient (IgE −/−) mice are dramatically reduced (by ∼83%) compared with those on cells from the corresponding normal mice. In vitro studies indicate that the IgE-dependent upregulation of mouse mast cell FcεRI 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 FcεRI 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 FcεRI 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.

Expression of a Functional FcεRI on Rat Eosinophils and Macrophages

“…Eosinophils were then analyzed by flow cytometry. Cells kept in culture for 4 days without IgE almost completely lost Fc⑀RI expression, as observed for mouse mast cells (45) (Fig. 5a), whereas in the presence of IgE, about 50% of the eosinophil population was expressing Fc⑀RI, albeit at a lower level than freshly isolated cells (Fig.…”

“…As described for mouse mast cells (42,45) and basophils (43) as well as for rat mast cells (44), receptor expression was up-regulated on eosinophils by incubation with its ligand. A very strong adherence of macrophages to culture wells during the 4-day incubation prevented us from assessing the phenomenon in this cell type.…”

Drastic Up-Regulation of FcεRI on Mast Cells Is Induced by IgE Binding Through Stabilization and Accumulation of FcεRI on the Cell Surface

“…However, Fc⑀RI expression could be up-regulated up to 32-fold by in vitro incubation of mast cells with IgE or by injection of IgE in vivo (14,15). Therefore, IgE-mediated Fc⑀RI up-regulation is not an artifact observed in cultured cell lines.…”

“…It was recently reported that levels of Fc⑀RI expression on mast cells freshly isolated from IgE-deficient mice were extremely low (20% of normal level) (14). However, Fc⑀RI expression could be up-regulated up to 32-fold by in vitro incubation of mast cells with IgE or by injection of IgE in vivo (14,15).…”

Oxysterol represses high‐affinity IgE receptor‐stimulated mast cell activation in Liver X receptor‐dependent and ‐independent manners

“…Because cell-surface FceRI expression is a critical element in the FceRI-dependent mast cell response [10], we examined the mechanism for down-regulation of FceRI by 25-OHC. As shown in Fig.…”