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

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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.