IgE and mast cells in allergic disease
ABSTRACT Immunoglobulin E (IgE) antibodies and mast cells have been so convincingly linked to the pathophysiology of anaphylaxis and other acute allergic reactions that it can be difficult to think of them in other contexts. However, a large body of evidence now suggests that both IgE and mast cells are also key drivers of the long-term pathophysiological changes and tissue remodeling associated with chronic allergic inflammation in asthma and other settings. Such potential roles include IgE-dependent regulation of mast-cell functions, actions of IgE that are largely independent of mast cells and roles of mast cells that do not directly involve IgE. In this review, we discuss findings supporting the conclusion that IgE and mast cells can have both interdependent and independent roles in the complex immune responses that manifest clinically as asthma and other allergic disorders.
- SourceAvailable from: Dongwoo Khang
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- "Allergic symptoms such as edema, warmth, and erythema are resulted from vasodilation and an increase of vascular permeability caused by histamine . (Galli and Tsai, 2012) In the histamine and β-hexosaminidase assay using cell line (RBL-2H3) and primary cells (RPMCs), TMB strongly inhibited mast cell degranulation. OVA-induced ASA and IgE-mediated PCA models are positively associated with histamine release from mast cells. "
ABSTRACT: As the importance of allergic disorders such as atopic dermatitis and allergic asthma, research on potential drug candidates becomes more necessary. Mast cells play an important role as initiators of allergic responses through the release of histamine; therefore, they should be the target of pharmaceutical development for the management of allergic inflammation. In our previous study, anti-allergic effect of extracts of Amomum xanthioides was demonstrated. To further investigate improved candidates, 1,2,4,5-tetramethoxybenzene (TMB) was isolated from methanol extracts of A. xanthioides. TMB dose-dependently attenuated the degranulation of mast cells without cytotoxicity by inhibiting calcium influx. TMB decreased the expression of pro-inflammatory cytokines such as tumor necrosis factor-α and interleukin (IL)-4 at both the transcriptional and translational levels. Increased expression of these cytokines was caused by translocation of nuclear factor-κB into the nucleus, and it was hindered by suppressing activation of IκB kinase complex. To confirm the effect of TMB in vivo, the ovalbumin (OVA)-induced active systemic anaphylaxis (ASA) and IgE-mediated passive cutaneous anaphylaxis (PCA) models were used. In the ASA model, hypothermia was decreased by oral administration of TMB, which attenuated serum histamine, OVA-specific IgE, and IL-4 levels. Increased pigmentation of Evans blue was reduced by TMB in a dose-dependent manner in the PCA model. Our results suggest that TMB is a possible therapeutic candidate for allergic inflammatory diseases that acts through the inhibition of mast cell degranulation and expression of pro-inflammatory cytokines. Copyright © 2015. Published by Elsevier Inc.Toxicology and Applied Pharmacology 05/2015; DOI:10.1016/j.taap.2015.05.006 · 3.63 Impact Factor
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- "In aggregate, the notion remains that S1P may serve as a pro-inflammatory signal by promoting T cell effector differentiation and by suppressing T-regs, a T cell subset that also modulates antigen-induced responses in mast cells (Gri et al., 2008). This may be particularly relevant in cases of recurrent allergic reactions such as those seen with allergic asthma (Galli and Tsai, 2012), where repeated increases in S1P (and other mediators) produced by mast cells can thus contribute to chronic inflammation. In addition, the repeated challenges inherent to chronic allergic diseases cause tissue remodeling characterized by epithelial cell injury and structural changes in vascular, smooth muscle and connective tissues, many of which have been shown to be affected by S1P (reviewed in (Ryan and Spiegel, 2008)). "
ABSTRACT: Sphingosine-1phosphate (S1P), platelet activating factor (PAF) and eicosanoids are bioactive lipid mediators abundantly produced by antigen-stimulated mast cells that exert their function mostly through specific cell surface receptors. Although it has long been recognized that some of these bioactive lipids are potent regulators of allergic diseases, their exact contributions to disease pathology have been obscured by the complexity of their mode of action and the regulation of their metabolism. Indeed, the effects of such lipids are usually mediated by multiple receptor subtypes that may differ in their signaling mechanisms and functions. In addition, their actions may be elicited by cell surface receptor-independent mechanisms. Furthermore, these lipids may be converted into metabolites that exhibit different functionalities, adding another layer of complexity to their overall biological responses. In some instances, a second wave of lipid mediator synthesis by both mast cell and non-mast cell sources may occur late during inflammation, bringing about additional roles in the altered environment. New evidence also suggests that bioactive lipids in the local environment can fine-tune mast cell maturation and phenotype, and thus their responsiveness. A better understanding of the subtleties of the spatiotemporal regulation of these lipid mediators, their receptors and functions may aid in the pursuit of pharmacological applications for allergy treatments. Copyright © 2015. Published by Elsevier B.V.European journal of pharmacology 05/2015; DOI:10.1016/j.ejphar.2015.02.058 · 2.68 Impact Factor
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- "Recently developed anti-IgE preventive therapies that neutralize circulating IgE or deplete IgE-producing cells have demonstrated some efficacy. However, clinical indications for these treatments have been limited to allergic asthma, chronic idiopathic urticarial , and rhinitis (Galli and Tsai, 2012; Gauvreau et al., 2014; Saini et al., 2015). Thus, the IgE oligomannose may be a potential therapeutic target for both cell-bound and circulating IgE. "
ABSTRACT: Immunoglobulin ε (IgE) antibodies are the primary mediators of allergic diseases, which affect more than 1 in 10 individuals worldwide. IgE specific for innocuous environmental antigens, or allergens, binds and sensitizes tissue-resident mast cells expressing the high-affinity IgE receptor, FcεRI. Subsequent allergen exposure cross-links mast cell-bound IgE, resulting in the release of inflammatory mediators and initiation of the allergic cascade. It is well established that precise glycosylation patterns exert profound effects on the biological activity of IgG. However, the contribution of glycosylation to IgE biology is less clear. Here, we demonstrate an absolute requirement for IgE glycosylation in allergic reactions. The obligatory glycan was mapped to a single N-linked oligomannose structure in the constant domain 3 (Cε3) of IgE, at asparagine-394 (N394) in human IgE and N384 in mouse. Genetic disruption of the site or enzymatic removal of the oligomannose glycan altered IgE secondary structure and abrogated IgE binding to FcεRI, rendering IgE incapable of eliciting mast cell degranulation, thereby preventing anaphylaxis. These results underscore an unappreciated and essential requirement of glycosylation in IgE biology. © 2015 Shade et al.Journal of Experimental Medicine 03/2015; 212(4). DOI:10.1084/jem.20142182 · 13.91 Impact Factor