IGE ENHANCES MOUSE MAST-CELL FC-EPSILON-RI EXPRESSION IN-VITRO AND IN-VIVO - EVIDENCE FOR A NOVEL AMPLIFICATION MECHANISM IN IGE-DEPENDENT REACTIONS

The binding of immunoglobulin E (IgE) to high affinity IgE receptors ( Fc epsilon RI) expressed on the surface of mast cells primes these cel ls to secrete, upon subsequent exposure to specific antigen, a panel o f proinflammatory mediators, which includes cytokines that can also ha ve immunoregulatory activities. This IgE- and antigen-specific mast ce ll activation and mediator production is thought to be critical to the pathogenesis of allergic disorders, such as anaphylaxis and asthma, a nd also contributes to host defense against parasites. We now report t hat 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 o r in vivo. Moreover, baseline levels of Fc epsilon RI expression on pe ritoneal mast cells from genetically IgE-deficient (IgE -/-) mice are dramatically reduced (by similar to 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 expressio n has two components: an early cycloheximide-insensitive phase, follow ed by a later and more sustained component that is highly sensitive to inhibition by cycloheximide. In turn, IgE-dependent upregulation of F c epsilon RI expression significantly enhances the ability of mouse ma st cells to release serotonin, interleukin-6 (IL-6), and IL-4 in respo nse to challenge with IgE and specific antigen. The demonstration that IgE-dependent enhancement of mast cell Fc epsilon RI expression permi ts mast cells to respond to antigen challenge with increased productio n of proinflammatory and immunoregulatory mediators provides new insig hts into both the pathogenesis of allergic diseases and the regulation of protective host responses to parasites.