Inhibitory effects of a cationic liposome on allergic reaction mediated by mast cell activation.
Inhibitory effects of a cationic liposome on allergic reaction mediated by mast cell activation.
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DOI：
10.1016/j.bcp.2013.09.023
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发表时间：
2013-12
影响因子：
5.8
通讯作者：
Yoshikazu Inoh;S. Tadokoro;H. Tanabe;M. Inoue;N. Hirashima;M. Nakanishi;T. Furuno
中科院分区：
文献类型：
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作者：
Yoshikazu Inoh;S. Tadokoro;H. Tanabe;M. Inoue;N. Hirashima;M. Nakanishi;T. Furuno
多项研究表明，阳离子脂质体具有免疫调节作用，具有低免疫原性和低毒性，制备方便、靶向性好等优点。阳离子脂质体不仅可以将DNA转运到免疫细胞，还可以增强树突状细胞和巨噬细胞等抗原提呈细胞的功能。在这里，我们研究了一种特殊的阳离子脂质体在过敏反应中对肥大细胞功能的影响。我们发现，与肥大细胞表面结合的阳离子脂质体以时间和剂量依赖的方式抑制高亲和免疫球蛋白E受体交联诱导的脱颗粒。对脱颗粒的抑制是通过抑制储存操作的Ca2+进入引起的细胞内Ca2+浓度（[Ca2+]i）持续水平的损害介导的。[Ca2+]持续升高的降低是由于可溶性乙基马来酰亚胺敏感因子附着蛋白受体蛋白（如SNAP-23， syntaxin-4）磷酸化的抑制，这些蛋白是在脱粒过程中分泌颗粒与质膜之间的膜融合所必需的。此外，阳离子脂质体还能抑制肥大细胞活化引起的小鼠血管通透性升高。这些结果表明，阳离子脂质体具有抑制肥大细胞活化的新特性，提示开发阳离子脂质体作为抗过敏效应剂的可能性。
Several studies have shown that cationic liposomes exert immunomodulatory effects with low immunogenicity and toxicity, and offer advantages such as easy preparation and targeting. Cationic liposomes not only transport DNA to immune cells but also enhance the function of antigen presenting cells such as dendritic cells and macrophages. Here, we investigated the effect of a particular cationic liposome on mast cell function during allergic reaction. We found that the cationic liposomes bound to the mast cell surface suppressed degranulation induced by cross-linking of high affinity immunoglobulin E receptors in a time- and dose-dependent manner. The suppression of degranulation was mediated by impairment of the sustained level of intracellular Ca2+concentration ([Ca2+]i) derived from the inhibition of store-operated Ca2+entry. The decrease in sustained elevation of [Ca2+]iled to the suppression of phosphorylation of solubleN-ethylmaleimide-sensitive factor attachment protein receptor proteins such as SNAP-23, syntaxin-4, which are necessary for membrane fusion between secretory granules and the plasma membrane during degranulation. Furthermore, the cationic liposomes suppressed vascular permeability elevation induced by mast cell activation in mice. These results showed that cationic liposomes possess the novel property of inhibiting mast cell activation, suggesting the possibility of developing cationic liposomes as anti-allergic effectors.