Histamine-releasing factor has a proinflammatory role in mouse models of asthma and allergy

Authors:
  • TATomoaki Ando
    Tomoaki Ando
  • KMKenji Matsumoto
    Kenji Matsumoto
  • MKMiho Kimura
    Miho Kimura
  • JKJiro Kitaura
    Jiro Kitaura
  • MMMichael H. Matho
    Michael H. Matho
  • DZDirk M. Zajonc
    Dirk M. Zajonc
  • TOTomomitsu Ozeki
    Tomomitsu Ozeki
  • CRChisei Ra
    Chisei Ra
  • SMSusan M. MacDonald
    Susan M. MacDonald
  • RSReuben P. Siraganian
    Reuben P. Siraganian
  • DBDavid H. Broide
    David H. Broide
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Abstract
IgE-mediated activation of mast cells and basophils underlies allergic diseases such as asthma. Histamine-releasing factor (HRF; also known as translationally controlled tumor protein [TCTP] and fortilin) has been implicated in late-phase allergic reactions (LPRs) and chronic allergic inflammation, but its functions during asthma are not well understood. Here, we identified a subset of IgE and IgG antibodies as HRF-interacting molecules in vitro. HRF was able to dimerize and bind to Igs via interactions of its N-terminal and internal regions with the Fab region of Igs. Therefore, HRF together with HRF-reactive IgE was able to activate mast cells in vitro. In mouse models of asthma and allergy, Ig-interacting HRF peptides that were shown to block HRF/Ig interactions in vitro inhibited IgE/HRF-induced mast cell activation and in vivo cutaneous anaphylaxis and airway inflammation. Intranasally administered HRF recruited inflammatory immune cells to the lung in naive mice in a mast cell– and Fc receptor–dependent manner. These results indicate that HRF has a proinflammatory role in asthma and skin immediate hypersensitivity, leading us to suggest HRF as a potential therapeutic target.

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