C5a receptor 1-/- mice are protected from the development of IgE-mediated experimental food allergy.
Authors of this article are:
Kordowski A, Reinicke AT, Wu D, Orinska Z, Hagemann P, Huber-Lang M, Lee JB, Wang YH, Hogan SP, Köhl J.
A summary of the article is shown below:
BACKGROUND: Food-induced anaphylaxis is a serious allergic reaction caused by Fcε-receptor activation on mast cells (MCs). The exact mechanisms breaking oral tolerance and the effector pathways driving food allergy remain elusive. As complement is activated in food-induced anaphylaxis, we aimed to assess the role of C5a in disease pathogenesis.METHODS: Oral antigen-induced food-induced anaphylaxis was induced in BALB/c wildtype (wt) and C5ar1-/- mice. Readouts included diarrhea development, changes in rectal temperature, hematocrit, antigen-specific serum IgE, MCPT-1 and intestinal MC numbers as well as FcεR1-mediated MC functions including C5a receptor 1 (C5aR1) regulation. Further, histamine-mediated hypothermia and regulation of endothelial tight junctions were determined.RESULTS: Repeated oral OVA challenge resulted in diarrhea, hypothermia, increased hematocrit, high OVA-specific serum IgE and MCPT-1 levels in wt mice. Male C5ar1-/- mice were completely whereas female C5ar1-/- were partially protected from anaphylaxis development. Serum MCPT-1 levels were reduced gender-independent, whereas IgE levels were reduced in male but not in female C5ar1-/- mice. Mechanistically, IgE-mediated degranulation and IL-6 production from C5ar1-/- BMMCs of both sexes were significantly reduced. Importantly, FcεR1 cross-linking strongly upregulated C5aR1 MC expression in vitro and in vivo. Finally, C5ar1-/- male mice were largely protected from histamine-induced hypovolemic shock, which was associated with protection from histamine-induced barrier dysfunction in vitro following C5aR targeting.CONCLUSIONS: Our findings identify C5aR1 activation as an important driver of IgE-mediated food allergy through regulation of allergen specific IgE production, FcεR1-mediated MC degranulation and histamine-driven effector functions preferentially in male mice. This article is protected by copyright. All rights reserved.This article is protected by copyright. All rights reserved.
Check out the article’s website on Pubmed for more information:
This article is a good source of information and a good way to become familiar with topics such as:
Complement;IgE;food allergy;histamine;mast cell
Categories: Science News