Angiopoietin1 inhibits mast cell activation and protects against anaphylaxis.

Angiopoietin1 inhibits mast cell activation and protects against anaphylaxis.
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血管生成素 1 抑制肥大细胞激活并预防过敏反应

DOI:
10.1371/journal.pone.0089148
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发表时间:
2014
期刊:
影响因子:
3.7
通讯作者:
Bai Y
Bai Y
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Yao JH;Cui M;Li MT;Liu YN;He QH;Xiao JJ;Bai Y

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由于过敏性疾病的发病率和死亡率逐年上升,如何有效地预防和管理这些疾病已成为一个重要的问题。肥大细胞在变态反应性疾病中起着重要的调节作用。血管生成素1(Ang-I)通过抑制血管通透性、白细胞迁移和细胞因子产生而表现出抗炎特性。然而,Ang-1在肥大细胞活化和过敏性疾病中的功能尚不清楚。我们的研究结果表明,Ang-1通过抑制IκB磷酸化和NF-κB核转位,减少脂多糖(LPS)诱导的肥大细胞产生促炎细胞因子。Ang-1还通过降低细胞内钙离子水平,强烈抑制化合物48/80诱导和Fcε RI介导的肥大细胞脱颗粒。在小鼠体内慢病毒介导的Ang-1递送表现出减轻IgE依赖性被动皮肤过敏反应(PCA)的渗漏。此外,外源性Ang-1干预治疗防止了小鼠由化合物48/80诱导的肠系膜肥大细胞脱颗粒,减弱了促炎细胞因子的增加,减轻了肺损伤,并改善了过敏性休克中的存活率。我们的研究结果首次揭示了Ang-1在肥大细胞活化中的重要作用,并确定了Ang-1对过敏性疾病的治疗作用。
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.
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