Activated platelets and endothelial cell interaction with neutrophils under flow conditions

Objective The mechanism of neutrophil adhesion to the endothelium during th e earliest stages of acute inflammation, especially before the induction of adhesion molecules on endothelial cells, remains unknown. We studied the p ossible involvement of platelets in this process. Methods Neutrophils were added to human umbilical vein-derived endothelial cells (HUVEC) with or without adherent platelets in the presence or absence of adhesion-blocking monoclonal antibodies (mAbs). Adhesion of neutrophils to HUVEC at dynamic flow conditions was assessed using a flow chamber. Results 1) Thrombin-activated platelets adhered to resting-HUVEC at dynamic flow conditions through platelet glycoprotein Ilb/IIIa and RGD proteins. 2 ) Neutrophils tethered to P-selectin induced on thrombin-activated platelet s, which were immobilized on HUVEC. 3) Activated neutrophils adhered, via L FA-1, to ICAM-1 on HUVEC. 4) Activated platelets induced interleukin (IL)-8 secretion by HUVEC. Conclusions Immobilized platelets on the vessel wall with induced P-selecti n on the surface biochemically and functionally promote the adhesion of neu trophils to endothelial cells.