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 the
impact of these interactions on platelet MMP-2 secretion and function in platelet
and neutrophil aggregation. The secretion of MMP-2 from human platelets was significantly
increased threefold after thrombin activation, and enhanced two-fold in the presence
of neutrophils. Neutrophil supernatant had no effect on platelet MMP-2 secretion.
While no MMP-2 was detected in the supernatant of neutrophils, a high amount of MMP-9
was released by neutrophils, and remained unchanged upon thrombin activation or in
the presence of platelets. Platelet P-selectin, which increased significantly after
activation, triggered platelet binding to neutrophils that was completely inhibited
by P-selectin or PSGL-1 antagonists, and was reduced by 50% with a GPIIb/ IIIa antagonist.
P-selectin or PSGL-1 antagonism abolished the enhanced secretion of platelet MMP-2
in the presence of neutrophils and reduced platelet-neutrophil aggregation. Platelet
activation and binding to neutrophils enhance the secretion of platelet MMP-2 via
an adhesive interaction between P-selectin and PSGL-1, which contribute to increase
platelet-neutrophil aggregation.
Keywords
Platelets - leukocytes - cell adhesion molecules - metalloproteinases