Shear stress affects migration behavior of polymorphonuclear cells arrested on endothelium

Polymorphonuclear cell (PMN) transmigration across the TNF-alpha-stimulated endothelial cell (HUVEC) monolayer in the presence of shear flow was monit ored with time-lapse videotapes. More than half of the PMN that arrested on HUVEC transmigrated through endothelial cell junctions within the followin g 15 min. The kinetics of transmigration was significantly faster than that of PMN placed under static conditions. Once PMN crept into the subendothel ial space, they showed random migration beneath the HUVEC monolayer. PMN th at did not transmigrate moved on the apical surface of HUVEC in the directi on of flow down stream. Anti-beta 1 integrin mAb (4B4) and RGD peptide inhi bited the transmigration more effectively than anti-beta 2 integrin mAb (TS 1/18) and almost totally abrogated transmigration. When HUVEC were cultured on fibronectin or laminin, the transmigration was significantly inhibited by anti-alpha 5 or alpha 6 integrin mAbs, respectively. Our data clearly in dicate that shear stress affects the migration behavior of PMN arrested on endothelium and suggest that binding to subendothelial extracellular matrix via beta 1 integrins is another essential step in leukocyte extravasation. (C) 2000 Academic Press.