IgE- and IgE+Ag-mediated mast cell migration in an autocrine/paracrine fashion

IgE- and IgE+Ag-mediated mast cell migration in an autocrine/paracrine fashion
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DOI:
10.1182/blood-2004-11-4205
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发表时间:
2005-04-15
期刊:
影响因子:
20.3
通讯作者:
Kawakami, T
Kawakami, T
中科院分区:
医学1区
文献类型:
--
作者:
Kitaura, J;Kinoshita, T;Kawakami, T

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肥大细胞是即刻过敏和慢性变态反应的主要效应细胞。这些细胞聚集在过敏反应的粘膜组织中,在那里局部产生免疫球蛋白E(IgE)。在这里,我们提供的证据表明,除了可以吸引IgE结合的肥大细胞的抗原外,能够有效激活肥大细胞的IgE分子类型还可以在没有抗原的情况下促进肥大细胞的迁移。IgE和IgE+Ag介导的迁移涉及腺苷、白三烯B-4和几种趋化因子等可溶性因子的自分泌/旁分泌。它们的分泌依赖于2个酪氨酸激酶,Lyn和Syk,它们是G蛋白偶联受体的激动剂,并通过磷脂酰肌醇3-激酶伽马传递信号,导致肥大细胞迁移。在小鼠实验中,幼稚的肥大细胞被IgE吸引,而IgE致敏的肥大细胞被抗原吸引。因此,IgE和抗原与局部高IgE水平的过敏组织部位的肥大细胞聚集有关。
Mast cells are the major effector cells for immediate hypersensitivity and chronic allergic reactions. These cells accumulate in mucosal tissues of allergic reactions, where immunoglobulin E (IgE) is produced locally. Here we provide evidence that, in addition to antigen that can attract IgE-bound mast cells, the type of IgE molecules that efficiently activate mast cells can promote the migration of mast cells in the absence of antigen. IgE and IgE+Ag-mediated migration involves an autocrine/paracrine secretion of soluble factors including adenosine, leukotriene B-4, and several chemokines. Their secretion depends on 2 tyrosine kinases, Lyn and Syk, and they are agonists of G-protein-coupled receptors and signal through phosphaticlylinositol 3-kinase gamma, leading to mast cell migration. In mouse experiments, naive mast cells are attracted to IgE, and IgE-sensitized mast cells are attracted to antigen. Therefore, IgE and antigen are implicated in mast cell accumulation at allergic tissue sites with local high IgE levels.