title: Histamine-releasing factor has a proinflammatory role in mouse models of asthma and allergy.
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.
authors: Division of Cell Biology, La Jolla Institute for Allergy and Immunology, La Jolla, California 92037, USA.
authors: Jun-chi
authors: JC
authors: Kashiwakura
authors: Tomoaki
authors: T
authors: Ando
authors: Kenji
authors: K
authors: Matsumoto
authors: Miho
authors: M
authors: Kimura
authors: Jiro
authors: J
authors: Kitaura
authors: Michael H
authors: MH
authors: Matho
authors: Dirk M
authors: DM
authors: Zajonc
authors: Tomomitsu
authors: T
authors: Ozeki
authors: Chisei
authors: C
authors: Ra
authors: Susan M
authors: SM
authors: MacDonald
authors: Reuben P
authors: RP
authors: Siraganian
authors: David H
authors: DH
authors: Broide
authors: Yuko
authors: Y
authors: Kawakami
authors: Toshiaki
authors: T
authors: Kawakami
mesh_terms: D000818:Animals; D001249:Asthma / Q000209:etiology* / Q000276:immunology / Q000517:prevention & control; D001491:Basophils / Q000276:immunology; D014408:Biomarkers, Tumor / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000276:immunology* / Q000502:physiology; D019281:Dimerization; D004195:Disease Models, Animal; D006967:Hypersensitivity / Q000209:etiology* / Q000276:immunology; D007073:Immunoglobulin E / Q000378:metabolism; D007140:Immunoglobulin Fab Fragments / Q000378:metabolism; D007074:Immunoglobulin G / Q000378:metabolism; D018836:Inflammation Mediators / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000276:immunology* / Q000502:physiology; D008407:Mast Cells / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010323:Passive Cutaneous Anaphylaxis / Q000276:immunology; D054730:Protein Interaction Domains and Motifs; D000090324:Tumor Protein, Translationally-Controlled 1
chemical_list: D014408:Biomarkers, Tumor; D007140:Immunoglobulin Fab Fragments; D007074:Immunoglobulin G; D018836:Inflammation Mediators; C000715648:Tpt1 protein, mouse; D000090324:Tumor Protein, Translationally-Controlled 1; D007073:Immunoglobulin E