IgE and mast cells in allergic disease
Department of Pathology, Stanford University School of Medicine, California, USA. Nature medicine
(Impact Factor: 27.36).
05/2012; 18(5):693-704. DOI: 10.1038/nm.2755
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.
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Available from: Andrey Kartashov
- "Clinical symptoms of food allergy patients range from a mild skin reaction to lethal shock (Boyce et al., 2010; Sicherer and Sampson, 2010). The anaphylactic response to ingested food antigens usually results from the activation of intestinal mast cells (MCs) through food-specific IgE antibodies (Finkelman, 2007; Galli and Tsai, 2012). However, it is perplexing as to why only some patients and murine strains that acquire high amounts of dietary allergen-specific IgE develop a severe immediate intestinal hypersensitivity response that can result in life-threatening anaphylaxis. "
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ABSTRACT: Experimental IgE-mediated food allergy depends on intestinal anaphylaxis driven by interleukin-9 (IL-9). However, the primary cellular source of IL-9 and the mechanisms underlying the susceptibility to food-induced intestinal anaphylaxis remain unclear. Herein, we have reported the identification of multifunctional IL-9-producing mucosal mast cells (MMC9s) that can secrete prodigious amounts of IL-9 and IL-13 in response to IL-33, and mast cell protease-1 (MCPt-1) in response to antigen and IgE complex crosslinking, respectively. Repeated intragastric antigen challenge induced MMC9 development that required T cells, IL-4, and STAT6 transcription factor, but not IL-9 signals. Mice ablated of MMC9 induction failed to develop intestinal mastocytosis, which resulted in decreased food allergy symptoms that could be restored by adoptively transferred MMC9s. Finally, atopic patients that developed food allergy displayed increased intestinal expression of Il9- and MC-specific transcripts. Thus, the induction of MMC9s is a pivotal step to acquire the susceptibility to IgE-mediated food allergy.
Immunity 09/2015; 43(4). DOI:10.1016/j.immuni.2015.08.020 · 21.56 Impact Factor
Available from: Dongwoo Khang
- "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. "
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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; 287(2). DOI:10.1016/j.taap.2015.05.006 · 3.71 Impact Factor
Available from: Ana Olivera
- "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)). "
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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 · 2.53 Impact Factor
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