Polymorphonuclear leukocyte adhesion to endothelial cells is inhibited by resting platelets

Abstract

The effect of human platelets on the adhesion of polymorphonuclear leukocytes (PMNs) to cultured endothelial cells was investigated. Resting platelets inhibited the adhesion of PMNs stimulated by JV.formyl-methionyl-leucyl-phenylalanine (fMLP), leukotriene B4 (LTB4), and tumor necrosis factor-α (TNF-α). Platelets similarly inhibited PMN adhesion induced by endothelial cell activation with TNF-α. The inhibitory effect depended on platelet number, was not associated with detectable platelet activation, and was also exerted by paraformaldehyde-fixed platelets. Moreover, supernatants of U46619- or thrombin-stimulated platelets were ineffective, thus excluding a role for constituents released as a result of the platelet-release reaction. Strong inhibition of PMN adhesion was exerted by platelet lysates. The inhibitory activity associated with lysates was sedimentable, heat sensitive, and not dialyzable through a membrane with a molecular-weight cutoff of 8,000; it was directed toward PMNs and was not due to cytotoxic effects or a general inhibition of PMN responsiveness to stimulation, since enzymatic release from activated PMNs was unaffected by platelet lysates. Finally, the activity was not prevented by specific adenosine inhibitors and anti-P-selectin monoclonal antibody. These data suggest that resting platelets can exert an inhibitory effect on PMN adhesion to the vessel wall during inflammatory and thrombotic conditions.