Summary

Platelets and neutrophils constitute a high source of metalloproteinases(MMPs), and their interactions via P-selectin and Pselectin-glycoprotein-ligand-1 (PSGL-1) are involved in thrombosis,vascular remodelling, and restenosis.We investigated theimpact of these interactions on platelet MMP-2 secretion andfunction in platelet and neutrophil aggregation.The secretion ofMMP-2 from human platelets was significantly increased threefoldafter thrombin activation, and enhanced two-fold in thepresence of neutrophils. Neutrophil supernatant had no effecton platelet MMP-2 secretion.While no MMP-2 was detected inthe supernatant of neutrophils, a high amount of MMP-9 was releasedby neutrophils, and remained unchanged upon thrombin activation or in the presence of platelets. Platelet P-selectin,which increased significantly after activation, triggered plateletbinding to neutrophils that was completely inhibited by P-selectinor PSGL-1 antagonists,and was reduced by 50% with a GPIIb/IIIa antagonist. P-selectin or PSGL-1 antagonism abolished theenhanced secretion of platelet MMP-2 in the presence of neutrophilsand reduced platelet-neutrophil aggregation. Plateletactivation and binding to neutrophils enhance the secretion ofplatelet MMP-2 via an adhesive interaction between P-selectinand PSGL-1, which contribute to increase platelet-neutrophilaggregation.