Proinflammatory role of histamine-releasing factor in asthma and allergy. Mus musculus

Immunoglobulin (Ig) E-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, is a highly conserved protein with both intracellular and extracellular functions. Secreted HRF can stimulate histamine release and IL-4 and IL-13 production from IgE-sensitized basophils and mast cells. HRF is found in nasal, skin blister and bronchoalveolar lavage (BAL) fluids during late-phase allergic reactions (LPRs), which implicates HRF in the LPR and chronic allergic inflammation. Here we identify a subset of IgE and IgG antibodies as HRF-interacting molecules. HRF can exist as a dimer and bind to immunoglobulins (Igs) via interactions of its N-terminal and internal regions with the Fab region of Igs. Therefore, HRF together with HRF-reactive IgE can activate mast cells in vitro. The Ig-interacting HRF peptides that block HRF-Ig interactions can inhibit IgE+HRF-induced mast cell activation and in vivo cutaneous anaphylaxis and airway inflammation. Intranasally administered HRF can recruit inflammatory immune cells to the lung in naïve mice in a mast cell- and Fc receptor-dependent manner. These results strongly suggest the proinflammatory role of HRF in asthma and skin immediate hypersensitivity. Overall design: A total of 6 samples were analyzed; wild type C57BL/6, FcRg KO and FceRIa KO mice were challenged with PBS (control) or mouse histamien-releasing factor