A NOVEL ROLE FOR E-SELECTIN AND P-SELECTIN - SHAPE CONTROL OF ENDOTHELIAL-CELL MONOLAYERS

The migration of neutrophils from blood vessels to peripheral tissues is a key step of inflammation, This requires the formation of transien t gaps between endothelial cells with concomitant leucocyte squeezing through these narrow apertures and immediate restoration of endotheliu m continuity. It is currently considered that the main role of selecti ns is to mediate the initial contact between flowing leucocytes and en dothelial cells. We show here that the binding of E- or P-selectins by specific antibodies induces a marked 'rounding up' of interleukin-1- or thrombin-activated human endothelial cells, respectively. Also, ant i-E-selectin antibodies trigger a transient increase in cytosolic calc ium involving intracellular calcium stores. No such effect is observed when von Willebrand factor or intercellular adhesion molecule 1 are s imilarly bound. Thus, in addition to promoting the initial interaction between activated endothelium and moving leucocytes, selectins might play a role in the induction of subsequent endothelial deformation, wh ich would facilitate leucocyte arrest and transmigration towards perip heral tissues, and enhance the diffusion of soluble molecules between intravascular and peripheral compartments. Our results are consistent, vith this hypothesis and demonstrate a new property of endothelial sel ectins.