The effect of Rho and FA for neutrophil transendothelial migration

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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. Recent studies suggest that 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, endothelial F-actin and myosin II rearrangement and endothelial MLC phosphorylation at selected times during the neutrophil migration, in vitro. The results showed that pretreating endothelial cells with C3 (Rho inhibitor) or Y-27632 (Rho kinase inhibitor) significantly diminished neutrophil migration, actin polymerization, myosin II filament formation, MLC phosphorylation, tyrosine phosphorylation of paxillin normally associated with the migration. These data suggest that endothelial Rho and Rho kinase regulate transendothelial neutrophil migration via tyrosine phosphorylation of focal adhesion by modulating the cytoskeletal events that mediate such migration.