Angiopoietin1 Inhibits Mast Cell Activation and Protects against Anaphylaxis

Abstract

Since morbidity and mortality rates of anaphylaxis diseases have been increasing year by year, how to prevent and manage these diseases effectively has become an important issue. Mast cells play a central regulatory role in allergic diseases. Angiopoietin1 (Ang-1) exhibits anti-inflammatory properties by inhibiting vascular permeability, leukocyte migration and cytokine production. However, Ang-1's function in mast cell activation and anaphylaxis diseases is unknown. The results of our study suggest that Ang-1 decreased lipopolysaccharide (LPS)-induced pro-inflammatory cytokines production of mast cells by suppressing IκB phosphorylation and NF-κB nuclear translocation. Ang-1 also strongly inhibited compound 48/80 induced and FcεRI-mediated mast cells degranulation by decreasing intracellular calcium levels in vitro. In vivo lentivirus-mediated delivery of Ang-1 in mice exhibited alleviated leakage in IgE-dependent passive cutaneous anaphylaxis (PCA). Furthermore, exogenous Ang-1 intervention treatment prevented mice from compound 48/80-induced mesentery mast cell degranulation, attenuated increases in pro-inflammatory cytokines, relieved lung injury, and improved survival in anaphylaxis shock. The results of our study reveal, for the first time, the important role of Ang-1 in the activation of mast cells, and identify a therapeutic effect of Ang-1 on anaphylaxis diseases.

Mutation of the angiopoietin-1 gene (ANGPT1) associates with a new type of hereditary angioedema

“…In animal studies an important role of ANGPT1 in the activation of mast cells that could be responsible for a therapeutic effect of ANGPT1 on anaphylaxis-related diseases was identified. 31 We have no evidence that the mutation reported in our patients could modify such a ''therapeutic'' effect of ANGPT1. However, recent data point to the possibility of an interplay between mast cell activation and kinin release during anaphylaxis and possibly angioedema.…”

Genome-wide association study and meta-analysis in multiple populations identifies new loci for peanut allergy and establishes C11orf30/EMSY as a genetic risk factor for food allergy

“…Some evidence suggests that lymphatic endothelial cells present self-antigens and help regulate peripheral T-cell tolerance. 54 Several identified loci from this study have connections to both allergy and vascular regulation (CTNNA3), 55 permeability (ANGPT4), 56,57 or endothelial cell function (SKAP1 58 and EXOC4 59 ). Their true role in the pathogenesis of allergic disease requires further research.…”

Imidacloprid inhibits IgE-mediated RBL-2H3 cell degranulation and passive cutaneous anaphylaxis

“…An IgE-dependent cutaneous reaction was carried out as described previously [30]. Anti-DNP IgE (500 ng/ear) was intradermally injected into a Balb/c mouse ear.…”