Regulation of interleukin-5-induced-β2-integrin adhesion of human eosinophils by phosphoinositide 3-kinase
Regulation of interleukin-5-induced-β2-integrin adhesion of human eosinophils by phosphoinositide 3-kinase
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DOI：
10.1165/rcmb.2005-0076oc
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发表时间：
2005-07-01
影响因子：
6.4
通讯作者：
Zhu, XD
中科院分区：
文献类型：
--
作者：
Sano, M;Leff, AR;Zhu, XD
我们研究了磷脂酰肌醇3-激酶（PI 3 K）在整合素介导的嗜酸性粒细胞粘附中的作用。Ap 85是IA类PI 3 K衔接子亚基的显性阴性形式，与HIV-TAT蛋白转导结构域（TAT-Ap 85）融合。重组TAT-Ap 85抑制白细胞介素（IL）-5刺激的蛋白激酶B（PI 3 K的下游靶点）的磷酸化。TAT-Ap 85以浓度依赖性方式抑制IL-5引起的β（2）-整合素依赖性粘附至接种的细胞内粘附分子-1替代物牛血清白蛋白。类似地，两种PI 3 K抑制剂渥曼青霉素和LY 294002阻断嗜酸性粒细胞与平板牛血清白蛋白的粘附。相比之下，PI-整合素介导的嗜酸性粒细胞与血管细胞粘附分子-1的粘附不被TAT-Δ p85、渥曼青霉素或LY 294002阻断。蛋白激酶C（PKC）-δ抑制剂Rottlerin也阻断IL-5引起的嗜酸性粒细胞的β（2）-整联蛋白粘附，而P1与血管细胞粘附分子-1的粘附不受影响。IL-5引起PKC δ从胞浆到细胞膜的易位; Wortmannin抑制PI 3 K阻断PKC δ的易位。蛋白质印迹分析表明，细胞外信号调节激酶磷酸化，一个关键的中介在由IL-5引起的粘附，被阻断的抑制PI 3 K或PKC-δ。这些数据表明，由IL-5引起的细胞外信号调节激酶介导的β（2）-整联蛋白的粘附在人嗜酸性粒细胞中由IA类PI 3 K通过激活PKC 8途径介导。
We examined the role of phosphoinositide 3-kinase (PI3K) in integrin-mediated eosinophil adhesion. Ap85, a dominant-negative form of the class IA PI3K adaptor subunit, was fused to an HIV-TAT protein transduction domain (TAT-Ap85). Recombinant TAT-Ap85 inhibited interleukin (IL)-5-stimulated phosphorylation of protein kinase B, a downstream target of PI3K. beta(2)-Integrin-dependent adhesion caused by IL-5 to the plated intracellular adhesion molecule-1 surrogate, bovine serum albumin, was inhibited by TAT-Ap85 in a concentration-dependent manner. Similarly, two PI3K inhibitors, wortmannin and LY294002, blocked eosinophil adhesion to plated bovine serum albumin. By contrast, PI-integrin-mediated eosinophil adhesion to vascular cell adhesion moelcule-1 was not blocked by TAT-Delta p85, wortmannin, or LY294002. Rottlerin, a protein kinase C (PKC)-delta inhibitor, also blocked beta(2)-integrin adhesion of eosinophils caused by IL-5, whereas P, adhesion to vascular cell adhesion molecule-1 was not affected. IL-5 caused translocation of PKC delta from the cytosol to cell membrane; inhibition of PI3K by wortmannin blocked translocation of PKC delta. Western blot analysis demonstrated that extracellular signal-regulated kinase phosphorylation, a critical intermediary in adhesion elicited by IL-5, was blocked by inhibition of either PI3K or PKC-delta. These data suggest that extracellular signal-regulated kinase-mediated adhesion Of beta(2)-integrin caused by IL-5 is mediated in human eosinophils by a class IA PI3K through activation of a PKC8 pathway.