Endothelial paxillin and focal adhesion kinase (FAK) play a critical role in neutrophil transmigration
Endothelial paxillin and focal adhesion kinase (FAK) play a critical role in neutrophil transmigration
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DOI：
10.1002/eji.201041303
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发表时间：
2012-02-01
影响因子：
5.4
通讯作者：
Patel, Kamala D.
中科院分区：
文献类型：
--
作者：
Parsons, Sean A.;Sharma, Ritu;Patel, Kamala D.
在炎症反应中，内皮细胞发生形态变化，允许中性粒细胞从血管到达损伤或感染部位。尽管内皮细胞连接和细胞骨架在炎症过程中进行重组，但对另一类细胞结构——局灶粘连却知之甚少。在这项研究中，我们在炎症反应中检测了几种局灶黏附蛋白。我们发现，在迁移中性粒细胞附近的局灶黏附中，帕西林和局灶黏附激酶（FAK）选择性丧失；相比之下，局灶黏附蛋白β 1-整合素和血管蛋白的水平不受影响。在静态和流动条件下，中性粒细胞迁移过程中，Paxillin因局灶粘连而丢失。用siRNA下调内皮细胞paxillin可阻断中性粒细胞迁移，但对滚动和粘附无影响。由于paxillin动力学部分由FAK调节，FAK在中性粒细胞迁移中的作用采用两种互补的方法进行了研究。使用siRNA下调FAK总蛋白，而表达显性阴性的激酶缺陷FAK以阻断FAK信号传导。FAK蛋白或FAK信号的破坏可减少中性粒细胞的转运。总的来说，这些发现揭示了内皮局灶黏附蛋白paxillin和FAK在调节中性粒细胞迁移中的新作用。
During an inflammatory response, endothelial cells undergo morphological changes to allow for the passage of neutrophils from the blood vessel to the site of injury or infection. Although endothelial cell junctions and the cytoskeleton undergo reorganization during inflammation, little is known about another class of cellular structures, the focal adhesions. In this study, we examined several focal adhesion proteins during an inflammatory response. We found that there was selective loss of paxillin and focal adhesion kinase (FAK) from focal adhesions in proximity to transmigrating neutrophils; in contrast the levels of the focal adhesion proteins beta 1-integrin and vinculin were unaffected. Paxillin was lost from focal adhesions during neutrophil transmigration both under static and flow conditions. Down-regulating endothelial paxillin with siRNA blocked neutrophil transmigration while having no effect on rolling or adhesion. As paxillin dynamics are regulated partly by FAK, the role of FAK in neutrophil transmigration was examined using two complementary methods. siRNA was used to down-regulate total FAK protein while dominant-negative, kinase-deficient FAK was expressed to block FAK signaling. Disruption of the FAK protein or FAK signaling decreased neutrophil transmigration. Collectively, these findings reveal a novel role for endothelial focal adhesion proteins paxillin and FAK in regulating neutrophil transmigration.