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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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Serotonin (5-HT) release from BMCMCs exhibiting different levels of surface expression of FcεRI, after challenge with various concentrations of either specific antigen (DNP–HSA) or the calcium ionophore, A23187. WBB6F1 +/+ BMCMCs were cultured without IgE or  with ascites IgE at 0.005 or 5.0 μg/ml for 4 d before passive sensitization  and antigen challenge or challenge with A23187. Zero in the A23187 experiment refers to cells incubated without A23187 but in the highest concentration of vehicle used for these studies (DMSO at 0.1%). *P <0.05,  **P <0.001, versus corresponding values for cells cultured without IgE.  The data shown (mean ± SEM; n = 3 per point) are representative of the  results obtained in two separate experiments using WBB6F1 +/+ BMCMCs.
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Figure 5: Serotonin (5-HT) release from BMCMCs exhibiting different levels of surface expression of FcεRI, after challenge with various concentrations of either specific antigen (DNP–HSA) or the calcium ionophore, A23187. WBB6F1 +/+ BMCMCs were cultured without IgE or with ascites IgE at 0.005 or 5.0 μg/ml for 4 d before passive sensitization and antigen challenge or challenge with A23187. Zero in the A23187 experiment refers to cells incubated without A23187 but in the highest concentration of vehicle used for these studies (DMSO at 0.1%). *P <0.05, **P <0.001, versus corresponding values for cells cultured without IgE. The data shown (mean ± SEM; n = 3 per point) are representative of the results obtained in two separate experiments using WBB6F1 +/+ BMCMCs.

Mentions: The effect of a 4-d incubation with IgE on the ability of BMCMCs to release mediators in response to challenge with IgE and antigen did not reflect a general enhancement of the secretory responsiveness of the cells, in that there was no significant parallel increase in the ability of the cells to release 5-HT in response to stimulation with the calcium ionophore A23187 (Fig. 5). The results shown in Fig. 5 are representative of those obtained in two separate experiments with BMCMCs and one with peritoneal mast cells.


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)

Serotonin (5-HT) release from BMCMCs exhibiting different levels of surface expression of FcεRI, after challenge with various concentrations of either specific antigen (DNP–HSA) or the calcium ionophore, A23187. WBB6F1 +/+ BMCMCs were cultured without IgE or  with ascites IgE at 0.005 or 5.0 μg/ml for 4 d before passive sensitization  and antigen challenge or challenge with A23187. Zero in the A23187 experiment refers to cells incubated without A23187 but in the highest concentration of vehicle used for these studies (DMSO at 0.1%). *P <0.05,  **P <0.001, versus corresponding values for cells cultured without IgE.  The data shown (mean ± SEM; n = 3 per point) are representative of the  results obtained in two separate experiments using WBB6F1 +/+ BMCMCs.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC2196143&req=5

Figure 5: Serotonin (5-HT) release from BMCMCs exhibiting different levels of surface expression of FcεRI, after challenge with various concentrations of either specific antigen (DNP–HSA) or the calcium ionophore, A23187. WBB6F1 +/+ BMCMCs were cultured without IgE or with ascites IgE at 0.005 or 5.0 μg/ml for 4 d before passive sensitization and antigen challenge or challenge with A23187. Zero in the A23187 experiment refers to cells incubated without A23187 but in the highest concentration of vehicle used for these studies (DMSO at 0.1%). *P <0.05, **P <0.001, versus corresponding values for cells cultured without IgE. The data shown (mean ± SEM; n = 3 per point) are representative of the results obtained in two separate experiments using WBB6F1 +/+ BMCMCs.
Mentions: The effect of a 4-d incubation with IgE on the ability of BMCMCs to release mediators in response to challenge with IgE and antigen did not reflect a general enhancement of the secretory responsiveness of the cells, in that there was no significant parallel increase in the ability of the cells to release 5-HT in response to stimulation with the calcium ionophore A23187 (Fig. 5). The results shown in Fig. 5 are representative of those obtained in two separate experiments with BMCMCs and one with peritoneal mast cells.

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