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IgE enhances mouse mast cell Fc(epsilon)RI expression in vitro and in vivo: evidence for a novel amplification mechanism in IgE-dependent reactions.

Yamaguchi M, Lantz CS, Oettgen HC, Katona IM, Fleming T, Miyajima I, Kinet JP, Galli SJ - J. Exp. Med. (1997)

Bottom Line: 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.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 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02215, USA.

ABSTRACT
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.

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Upregulation of secretory  function of IgE −/− peritoneal mast  cells after administration of IgE in vivo.  Peritoneal cells were combined from  two of the IgE −/− mice that had been  treated with affinity-purified IgG2a  mAb and four of the IgE −/− mice that  had been treated with purified IgE mAb  from Fig. 7 C. IgE- and antigen-induced  5-HT release was determined for each  group of cells (n = 3 per point) as in  Fig. 4 B. ***P <0.0001 versus corresponding values for cells from IgG2atreated mice.
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Figure 9: Upregulation of secretory function of IgE −/− peritoneal mast cells after administration of IgE in vivo. Peritoneal cells were combined from two of the IgE −/− mice that had been treated with affinity-purified IgG2a mAb and four of the IgE −/− mice that had been treated with purified IgE mAb from Fig. 7 C. IgE- and antigen-induced 5-HT release was determined for each group of cells (n = 3 per point) as in Fig. 4 B. ***P <0.0001 versus corresponding values for cells from IgG2atreated mice.

Mentions: Next, we assessed baseline levels of FcεRI expression in peritoneal mast cells of untreated IgE −/− versus IgE +/+ mice, and found that FcεRI expression was reduced by ∼83% in mast cells from IgE −/− mice as compared with those from wild-type mice (Fig. 7 B). We also found that administration of IgE (but not IgG2a) antibody resulted in a marked increase in FcεRI expression by IgE −/− mouse peritoneal mast cells (compare Fig. 7, B and C), whereas treatment with either antibody had no significant effect on mast cell FcγRII/III expression (data not shown). Moreover, there was a strong positive correlation, in the mice shown in Fig. 7, A and C, between the log10 of the serum IgE concentration at sacrifice and levels of mast cell FcεRI expression (R = 0.871, P <0.0001) (Fig. 8). And when the peritoneal mast cells removed from the mice shown in Fig. 7 C were tested for their ability to release 5-HT upon antigen challenge in vitro, the response of mast cells from mice that had been injected with IgE was markedly enhanced compared with that of the control cells from the IgG2a-treated mice (Fig. 9).


IgE enhances mouse mast cell Fc(epsilon)RI expression in vitro and in vivo: evidence for a novel amplification mechanism in IgE-dependent reactions.

Yamaguchi M, Lantz CS, Oettgen HC, Katona IM, Fleming T, Miyajima I, Kinet JP, Galli SJ - J. Exp. Med. (1997)

Upregulation of secretory  function of IgE −/− peritoneal mast  cells after administration of IgE in vivo.  Peritoneal cells were combined from  two of the IgE −/− mice that had been  treated with affinity-purified IgG2a  mAb and four of the IgE −/− mice that  had been treated with purified IgE mAb  from Fig. 7 C. IgE- and antigen-induced  5-HT release was determined for each  group of cells (n = 3 per point) as in  Fig. 4 B. ***P <0.0001 versus corresponding values for cells from IgG2atreated mice.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC2196143&req=5

Figure 9: Upregulation of secretory function of IgE −/− peritoneal mast cells after administration of IgE in vivo. Peritoneal cells were combined from two of the IgE −/− mice that had been treated with affinity-purified IgG2a mAb and four of the IgE −/− mice that had been treated with purified IgE mAb from Fig. 7 C. IgE- and antigen-induced 5-HT release was determined for each group of cells (n = 3 per point) as in Fig. 4 B. ***P <0.0001 versus corresponding values for cells from IgG2atreated mice.
Mentions: Next, we assessed baseline levels of FcεRI expression in peritoneal mast cells of untreated IgE −/− versus IgE +/+ mice, and found that FcεRI expression was reduced by ∼83% in mast cells from IgE −/− mice as compared with those from wild-type mice (Fig. 7 B). We also found that administration of IgE (but not IgG2a) antibody resulted in a marked increase in FcεRI expression by IgE −/− mouse peritoneal mast cells (compare Fig. 7, B and C), whereas treatment with either antibody had no significant effect on mast cell FcγRII/III expression (data not shown). Moreover, there was a strong positive correlation, in the mice shown in Fig. 7, A and C, between the log10 of the serum IgE concentration at sacrifice and levels of mast cell FcεRI expression (R = 0.871, P <0.0001) (Fig. 8). And when the peritoneal mast cells removed from the mice shown in Fig. 7 C were tested for their ability to release 5-HT upon antigen challenge in vitro, the response of mast cells from mice that had been injected with IgE was markedly enhanced compared with that of the control cells from the IgG2a-treated mice (Fig. 9).

Bottom Line: 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.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 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02215, USA.

ABSTRACT
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.

Show MeSH
Related in: MedlinePlus