アレルギー炎症反応におけるヒスタミン遊離因子の役割  [in Japanese] Role of Histamine-releasing Factor in Allergic Inflammatory Reactions  [in Japanese]

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Author(s)

    • 柏倉 淳一 Kashiwakura Jun-ichi
    • 独立行政法人理化学研究所統合生命医科学研究センターアレルギー研究チーム|日本大学医学部医学教育企画・推進室免疫・アレルギー学プロジェクトチーム|Division of Cell Biology, La Jolla Institute for Allergy and Immunology Laboratory for Allergic Disease, RIKEN Center for Integrative Medical Sciences|Allergy and Immunology Project Team, Division of Medical Education Planning and Development, Nihon University School of Medicine|Division of Cell Biology, La Jolla Institute for Allergy and Immunology
    • 安藤 智暁 Ando Tomoaki
    • 独立行政法人理化学研究所統合生命医科学研究センターアレルギー研究チーム Laboratory for Allergic Disease, RIKEN Center for Integrative Medical Sciences
    • 川上 敏明 Kawakami Toshiaki
    • 独立行政法人理化学研究所統合生命医科学研究センターアレルギー研究チーム|Division of Cell Biology, La Jolla Institute for Allergy and Immunology Laboratory for Allergic Disease, RIKEN Center for Integrative Medical Sciences|Division of Cell Biology, La Jolla Institute for Allergy and Immunology

Abstract

 Mast cells are effector cells in immunoglobulin E (IgE)-mediated immediate hypersensitivity and allergic diseases such as asthma and food allergy. Mast cells are activated by the aggregation of the IgE-bound high-affinity IgE receptor FcεRI with multivalent antigen. Activated mast cells secrete proinflammatory mediators such as histamine, serotonin, and proteases and produce cytokines and chemokines. However, it has been reported that mast cells are activated by crosslinking of FcεRI with monomeric IgE in the absence of antigen. We have recently demonstrated that histamine-releasing factor (HRF) is involved in IgE-mediated mast cell activation both <i>in vitro</i> and <i>in vivo</i>. HRF binds to a subset of IgE and IgG molecules [HRF-reactive antibodies (Abs)]. The Fab, but not Fc, portions of the IgE and IgG molecules are HRF-binding sites, and the <i>N</i>-terminal 19-residue (N19) and H3 portions of HRF are HRF-reactive Ab-binding sites. We observed that both N19 and H3 tagged with glutathione S transferase (GST) (GST-N19 and GST-H3) can inhibit the interaction between HRF and HRF-reactive Abs. Using acute- and late-phase passive cutaneous anaphylaxis mouse models, it was shown that HRF initiates mast cell activation through HRF-reactive, but not HRF-nonreactive, IgE <i>in vivo</i>. Antigen-induced passive cutaneous anaphylaxis was inhibited by pretreatment with GST-N19 and GST-H3. We demonstrated that pretreatment with GST-N19 before antigen challenge inhibited antigen-induced mast cell-dependent airway inflammation. In addition, GST-N19 partially inhibited <i>Aspergillus fumigatus</i> extract-induced IgE-dependent airway inflammation. However, GST-N19 did not inhibit T cell-dependent airway inflammation. These results suggest that mast cells are target cells for HRF to initiate IgE- and mast cell-dependent airway inflammation.<br>

Journal

  • YAKUGAKU ZASSHI

    YAKUGAKU ZASSHI 137(5), 517-521, 2017

    The Pharmaceutical Society of Japan

Codes

  • NII Article ID (NAID)
    130005631392
  • NII NACSIS-CAT ID (NCID)
    AN00284903
  • Text Lang
    JPN
  • ISSN
    0031-6903
  • NDL Article ID
    028198377
  • NDL Call No.
    Z19-411
  • Data Source
    NDL  J-STAGE 
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