P-selectin mediates neutrophil adhesion to endothelial cell borders

During an acute inflammatory response, endothelial P-selectin (CD62P) can mediate the initial capture of neutrophils from the free flowing bloodstream. P-selectin is stored in secretory granules (Weibel-Palade bodies) amid is rapidly expressed on the endothelial surface after stimulation with histamine or thrombin. Because neutrophil transmigration occurs preferentially at endothelial borders, we wished to determine whether P-selectin-dependent neutrophil capture (adhesion) occurs at endothelial cell borders. Under static or hydrodynamic now (2 dyn/cm(2)) conditions,, histamine (10(-4) M) or thrombin (0.2 U/mL) treatment induced preferential (greater than or equal to 75%) neutrophil adhesion to the cell borders of endothelial monolayers, Blocking antibody studies established that neutrophil adhesion was completely P-selectin dependent. P-selectin surface expression increased significantly after histamine treatment and P-selectin immunostaining was concentrated along endothelial borders. We conclude that preferential P-selectin expression along endothelial herders may be an important mechanism for targeting neutrophil migration at endothelial borders.