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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.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.

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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Correlation of serum IgE concentration at sacrifice and surface FcεRI expression of peritoneal mast cells in  the mice from the experiments  depicted in Fig. 7 (A and C).  The genotypes of the mice, and  the treatment which they received (PBS, IgE, or IgG2a, i.v.  daily for 4 d) are depicted in the  symbol key in the figure. Note  that the correlation coefficient was  calculated based on all data except  those from IgG2a-treated IgE  −/− mice, which were devoid  of serum IgE; as a result, n = 22.
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Figure 8: Correlation of serum IgE concentration at sacrifice and surface FcεRI expression of peritoneal mast cells in the mice from the experiments depicted in Fig. 7 (A and C). The genotypes of the mice, and the treatment which they received (PBS, IgE, or IgG2a, i.v. daily for 4 d) are depicted in the symbol key in the figure. Note that the correlation coefficient was calculated based on all data except those from IgG2a-treated IgE −/− mice, which were devoid of serum IgE; as a result, n = 22.

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)

Correlation of serum IgE concentration at sacrifice and surface FcεRI expression of peritoneal mast cells in  the mice from the experiments  depicted in Fig. 7 (A and C).  The genotypes of the mice, and  the treatment which they received (PBS, IgE, or IgG2a, i.v.  daily for 4 d) are depicted in the  symbol key in the figure. Note  that the correlation coefficient was  calculated based on all data except  those from IgG2a-treated IgE  −/− mice, which were devoid  of serum IgE; as a result, n = 22.
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Related In: Results  -  Collection

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Figure 8: Correlation of serum IgE concentration at sacrifice and surface FcεRI expression of peritoneal mast cells in the mice from the experiments depicted in Fig. 7 (A and C). The genotypes of the mice, and the treatment which they received (PBS, IgE, or IgG2a, i.v. daily for 4 d) are depicted in the symbol key in the figure. Note that the correlation coefficient was calculated based on all data except those from IgG2a-treated IgE −/− mice, which were devoid of serum IgE; as a result, n = 22.
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.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.

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