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Histamine-releasing factor has a proinflammatory role in mouse models of asthma and allergy.
- Source :
-
Journal of Clinical Investigation . Jan2012, Vol. 122 Issue 1, p218-228. 11p. 7 Graphs. - Publication Year :
- 2012
-
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. [ABSTRACT FROM AUTHOR]
- Subjects :
- *MAST cells
*BASOPHILS
*ASTHMA
*HISTAMINE
*TUMOR proteins
Subjects
Details
- Language :
- English
- ISSN :
- 00219738
- Volume :
- 122
- Issue :
- 1
- Database :
- Academic Search Index
- Journal :
- Journal of Clinical Investigation
- Publication Type :
- Academic Journal
- Accession number :
- 70350460
- Full Text :
- https://doi.org/10.1172/JCI59072