title: 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.
authors.affiliation: Department of Cell Biology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China.
authors.forename: Jun-Hua
authors.initials: JH
authors.lastname: Yao
authors.affiliation: Department of Cardiology, Peking University Third Hospital, Beijing, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Cui
authors.affiliation: Department of Cell Biology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China.
authors.forename: Meng-Tao
authors.initials: MT
authors.lastname: Li
authors.affiliation: Department of Cell Biology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China.
authors.forename: Yi-Nan
authors.initials: YN
authors.lastname: Liu
authors.affiliation: Department of Cell Biology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China.
authors.forename: Qi-Hua
authors.initials: QH
authors.lastname: He
authors.affiliation: Department of Cell Biology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China.
authors.forename: Jun-Jun
authors.initials: JJ
authors.lastname: Xiao
authors.affiliation: Department of Cell Biology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Bai
mesh_terms: D000707:Anaphylaxis / Q000097:blood / Q000235:genetics / Q000276:immunology / Q000517:prevention & control*; D042683:Angiopoietin-1 / Q000494:pharmacology* / Q000502:physiology; D000818:Animals; D015550:Cell Degranulation / Q000187:drug effects; D002478:Cells, Cultured; D015536:Down-Regulation / Q000187:drug effects; D057809:HEK293 Cells; D006801:Humans; D007073:Immunoglobulin E / Q000502:physiology; D018836:Inflammation Mediators / Q000097:blood; D008070:Lipopolysaccharides; D008297:Male; D008407:Mast Cells / Q000187:drug effects* / Q000276:immunology*; D051379:Mice; D010323:Passive Cutaneous Anaphylaxis
chemical_list: D042683:Angiopoietin-1; C467628:Angpt1 protein, mouse; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D007073:Immunoglobulin E