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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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IgE can regulate levels of peritoneal mast cell FcεRI expression in vivo. (A) FcεRI expression in peritoneal mast cells from BALB/c  mice that had been treated for 4 d with a daily i.v. injection of 100 μg of  affinity-purified IgE (n = 7) or IgG2a (n = 6) mAb, or vehicle (PBS)  alone (n = 4). ***P <0.0001 or <0.005 versus values for PBS- or IgG2atreated mice, respectively. (B) Baseline levels of FcεRI expression on  peritoneal mast cells from IgE +/+ (n = 8) and IgE −/− (n = 7) mice.  ***P <0.0001 versus values for IgE +/+ cells. (C) FcεRI expression in  peritoneal mast cells from IgE −/− mice treated with purified IgE mAb  (n = 5) or purified IgG2a mAb (n = 4) as in (A). ***P <0.0001 versus values for cells from IgG2a-treated mice. All values in (A–C) are mean ± SEM.
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Figure 7: IgE can regulate levels of peritoneal mast cell FcεRI expression in vivo. (A) FcεRI expression in peritoneal mast cells from BALB/c mice that had been treated for 4 d with a daily i.v. injection of 100 μg of affinity-purified IgE (n = 7) or IgG2a (n = 6) mAb, or vehicle (PBS) alone (n = 4). ***P <0.0001 or <0.005 versus values for PBS- or IgG2atreated mice, respectively. (B) Baseline levels of FcεRI expression on peritoneal mast cells from IgE +/+ (n = 8) and IgE −/− (n = 7) mice. ***P <0.0001 versus values for IgE +/+ cells. (C) FcεRI expression in peritoneal mast cells from IgE −/− mice treated with purified IgE mAb (n = 5) or purified IgG2a mAb (n = 4) as in (A). ***P <0.0001 versus values for cells from IgG2a-treated mice. All values in (A–C) are mean ± SEM.

Mentions: 12–22-wk-old mice were used in four separate in vivo experiments, two with BALB/c mice (data combined in Fig. 7 A), one with untreated IgE −/− and corresponding IgE +/+ mice (Fig. 7 B), and one with antibodytreated IgE −/− mice (Fig. 7 C). Purified mouse IgG2a mAb (Sigma, clone UPC 10) and mouse anti-DNP IgE mAb (Sigma, clone SPE-7) were dialyzed to remove NaN3, centrifuged at 100,000 g for 1 h at 4°C, and filtered before use. For i.v. treatment, IgG2a or IgE (100 μg in 0.24 ml PBS) or 0.24 ml of PBS alone was administered to each mouse daily by tail vein. Blood was obtained at time of death (∼18 h after the last i.v. injection) for measurement of total serum IgE concentration by ELISA (28). For assay of serotonin release, peritoneal cells were incubated for 20 h in DMEM containing 10% FCS (27) and then sensitized with IgE, labeled with [3H]5-HT, and stimulated with DNP– HSA as described above.


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)

IgE can regulate levels of peritoneal mast cell FcεRI expression in vivo. (A) FcεRI expression in peritoneal mast cells from BALB/c  mice that had been treated for 4 d with a daily i.v. injection of 100 μg of  affinity-purified IgE (n = 7) or IgG2a (n = 6) mAb, or vehicle (PBS)  alone (n = 4). ***P <0.0001 or <0.005 versus values for PBS- or IgG2atreated mice, respectively. (B) Baseline levels of FcεRI expression on  peritoneal mast cells from IgE +/+ (n = 8) and IgE −/− (n = 7) mice.  ***P <0.0001 versus values for IgE +/+ cells. (C) FcεRI expression in  peritoneal mast cells from IgE −/− mice treated with purified IgE mAb  (n = 5) or purified IgG2a mAb (n = 4) as in (A). ***P <0.0001 versus values for cells from IgG2a-treated mice. All values in (A–C) are mean ± SEM.
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Related In: Results  -  Collection

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Figure 7: IgE can regulate levels of peritoneal mast cell FcεRI expression in vivo. (A) FcεRI expression in peritoneal mast cells from BALB/c mice that had been treated for 4 d with a daily i.v. injection of 100 μg of affinity-purified IgE (n = 7) or IgG2a (n = 6) mAb, or vehicle (PBS) alone (n = 4). ***P <0.0001 or <0.005 versus values for PBS- or IgG2atreated mice, respectively. (B) Baseline levels of FcεRI expression on peritoneal mast cells from IgE +/+ (n = 8) and IgE −/− (n = 7) mice. ***P <0.0001 versus values for IgE +/+ cells. (C) FcεRI expression in peritoneal mast cells from IgE −/− mice treated with purified IgE mAb (n = 5) or purified IgG2a mAb (n = 4) as in (A). ***P <0.0001 versus values for cells from IgG2a-treated mice. All values in (A–C) are mean ± SEM.
Mentions: 12–22-wk-old mice were used in four separate in vivo experiments, two with BALB/c mice (data combined in Fig. 7 A), one with untreated IgE −/− and corresponding IgE +/+ mice (Fig. 7 B), and one with antibodytreated IgE −/− mice (Fig. 7 C). Purified mouse IgG2a mAb (Sigma, clone UPC 10) and mouse anti-DNP IgE mAb (Sigma, clone SPE-7) were dialyzed to remove NaN3, centrifuged at 100,000 g for 1 h at 4°C, and filtered before use. For i.v. treatment, IgG2a or IgE (100 μg in 0.24 ml PBS) or 0.24 ml of PBS alone was administered to each mouse daily by tail vein. Blood was obtained at time of death (∼18 h after the last i.v. injection) for measurement of total serum IgE concentration by ELISA (28). For assay of serotonin release, peritoneal cells were incubated for 20 h in DMEM containing 10% FCS (27) and then sensitized with IgE, labeled with [3H]5-HT, and stimulated with DNP– HSA as described above.

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