The role of endothelial VASP for neutrophils transendothelial migration during acute inflammation.

中性粒细胞的跨内皮迁移是急性炎症反应的关键步骤，我们以前研究发现，中性粒细胞跨内皮迁移受内皮肌球蛋白轻链激酶的调控，Rho和Rho激酶也是肌球蛋白轻链（MLC）磷酸化的关键介质，但它们在中性粒细胞跨内皮迁移中的作用尚不清楚。在本研究中，transwell室迁移分析系统，将内皮细胞单层被用来检查的数量迁移中性粒细胞和内皮血管舒张刺激磷酸化，蛋白质负责控制肌动蛋白丝的几何形状，在选定的时间在中性粒细胞迁移，在体外。结果表明，羟乙基淀粉（HES）预处理内皮细胞可明显抑制中性粒细胞跨内皮迁移，蛋白激酶A抑制剂H89可抑制HES对中性粒细胞跨内皮迁移的影响，VASP磷酸化与抑制中性粒细胞跨内皮迁移有关。这些数据表明，内皮VASP调节跨内皮中性粒细胞迁移，通过调节介导这种迁移的细胞骨架事件。

The transendothelial migration of neutrophils is a critical step in acute inflammation, which we previously showed to be regulated by endothelial myosin light chain kinase, Rho and Rho kinase are also key mediators of myosin light chain (MLC) phosphorylation, but their roles in neutrophil migration has not been investigated. In the present study, a transwell chamber migration assay system incorporating endothelial monolayer was used to examined the numbers of migrating neutrophils and endothelial vasodilator-stimulated phopphorylation, a protein responsible for controlling the geometry of actin-filament, at selected times during the neutrophil migration, in vitro. The results showed that pretreating endothelial cells with hydroxyethyl starch (HES) significantly diminished neutrophil migration, H89 (protein kinase A inhibitor) inhibited the effect of HES on neutrophil transendothelial migration, and VASP phosphorylation normally associated with the inhibition of neutriphil transendothelial migration. These data suggest that endothelial VASP regulate transendothelial neutrophil migration by modulating the cytoskeletal events that mediate such migration.