Regulation of highly cytokinergic IgE-induced mast cell adhesion by Src, Syk, Tec, and protein kinase C family kinases
Regulation of highly cytokinergic IgE-induced mast cell adhesion by Src, Syk, Tec, and protein kinase C family kinases
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DOI：
10.4049/jimmunol.174.8.4495
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发表时间：
2005-04-15
影响因子：
4.4
通讯作者：
Kawakami, T
中科院分区：
文献类型：
--
作者：
Kitaura, J;Eto, K;Kawakami, T
肥大细胞在IgE依赖性速发型超敏反应中起关键作用。最近的研究表明，与传统观点相反，单体IgE与Fc ε RI的结合导致肥大细胞中的许多生物学结果，包括存活。然而，IgE分子在诱导细胞因子产生方面表现出异质性;高细胞分裂素（HC）IgE引起广泛的Fc β RI聚集，这导致存活和其他激活事件的有效增强，而低细胞分裂素（PC）IgE可能效率低下。本研究表明，HC，而不是PC，IgE可以有效地诱导小鼠肥大细胞的粘附和蔓延的纤连蛋白包被的板在缓慢和持续的动力学。HC IgE通过β（1）和β（7）整合素诱导粘附，促进存活、IL-6产生和DNA合成。重要的是，我们已经确定林恩和Syk作为必要的酪氨酸激酶和Hck，Btk，和蛋白激酶C 0作为贡献的激酶在HC IgE诱导的粘附和扩散，而蛋白激酶C β起着负面的作用。与这些结果一致，与用IgE和Ag刺激的细胞相比，林恩、Syk和Btk在HC IgE刺激的细胞中以较慢但更持续的方式被激活。因此，HC IgE与Fc ε RI的结合通过以独特的方式调节细胞活化信号诱导肥大细胞与纤连蛋白的粘附。
Mast cells play a critical role in IgE-dependent immediate hypersensitivity. Recent studies have shown that, contrary to the traditional view, binding of monomeric IgE to Fc epsilon RI results in a number of biological outcomes in mast cells, including survival. However, IgE molecules display heterogeneity in inducing cytokine production; highly cytokinergic (HC) IgEs cause extensive Fc epsilon RI aggregation, which leads to potent enhancement of survival and other activation events, whereas poorly cytokinergic (PC) IgEs can do so inefficiently. The present study demonstrates that HC, but not PC, IgEs can efficiently induce adhesion and spreading of mouse mast cells on fibronectin-coated plates in slow and sustained kinetics. HC IgE-induced adhesion through beta(1) and beta(7), integrins promotes survival, IL-6 production, and DNA synthesis. Importantly, we have identified Lyn and Syk as requisite tyrosine kinases and Hck, Btk, and protein kinase C 0 as contributory kinases in HC IgE-induced adhesion and spreading, whereas protein kinase C epsilon plays a negative role. Consistent with these results, Lyn, Syk, and Btk are activated in HC IgE-stimulated cells in a slower but more sustained manner, compared with cells stimulated with IgE and Ag. Thus, binding of HC IgEs to Fc epsilon RI induces adhesion of mast cells to fibronectin by modulating cellular activation signals in a unique fashion.