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Differential release of mast cell mediators and the pathogenesis of inflammation

Authors

  • Theoharis C. Theoharides,

    Corresponding author
    1. Laboratory of Molecular Immunopharmacology and Drug Discovery, Department of Pharmacology and Experimental Therapeutics, Tufts University School of Medicine and Tufts – New England Medical Center, Boston, MA, USA.
    2. Department of Biochemistry, Tufts University School of Medicine and Tufts – New England Medical Center, Boston, MA, USA.
    3. Department of Internal Medicine, Tufts University School of Medicine and Tufts – New England Medical Center, Boston, MA, USA.
    4. Allergy Section, Attikon Hospital, Athens, Medical School, Athens, Greece.
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  • Duraisamy Kempuraj,

    1. Laboratory of Molecular Immunopharmacology and Drug Discovery, Department of Pharmacology and Experimental Therapeutics, Tufts University School of Medicine and Tufts – New England Medical Center, Boston, MA, USA.
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  • Michael Tagen,

    1. Laboratory of Molecular Immunopharmacology and Drug Discovery, Department of Pharmacology and Experimental Therapeutics, Tufts University School of Medicine and Tufts – New England Medical Center, Boston, MA, USA.
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  • Pio Conti,

    1. Immunology Division, Department of Cancer and Neuroscience, Chieti University Medical School, Chieti, Italy.
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  • Dimitris Kalogeromitros

    1. Allergy Section, Attikon Hospital, Athens, Medical School, Athens, Greece.
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Errata

This article is corrected by:

  1. Errata: Corrigendum Volume 219, Issue 1, 204, Article first published online: 10 September 2007

Theoharis C. Theoharides, PhD, MD
Department of Pharmacology and Experimental Therapeutics Tufts University School of Medicine
136 Harrison Avenue
Boston, MA 02111, USA
Tel.: (617) 636 6866
Fax: (617) 636 2456
E-mail: theoharis.theoharides@tufts.edu

Abstract

Summary:  Mast cells are well known for their involvement in allergic and anaphylactic reactions, during which immunoglobulin E (IgE) receptor (FcɛRI) aggregation leads to exocytosis of the content of secretory granules (1000 nm), commonly known as degranulation, and secretion of multiple mediators. Recent findings implicate mast cells also in inflammatory diseases, such as multiple sclerosis, where mast cells appear to be intact by light microscopy. Mast cells can be activated by bacterial or viral antigens, cytokines, growth factors, and hormones, leading to differential release of distinct mediators without degranulation. This process appears to involve de novo synthesis of mediators, such as interleukin-6 and vascular endothelial growth factor, with release through secretory vesicles (50 nm), similar to those in synaptic transmission. Moreover, the signal transduction steps necessary for this process appear to be largely distinct from those known in FcɛRI-dependent degranulation. How these differential mast cell responses are controlled is still unresolved. No clinically available pharmacological agents can inhibit either degranulation or mast cell mediator release. Understanding this process could help develop mast cell inhibitors of selective mediator release with novel therapeutic applications.

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