Neutrophil P-selectin-glycoprotein-ligand-1 binding to platelet P-selectin enhances metalloproteinase 2 secretion and platelet-neutrophil aggregation.
Platelets and neutrophils constitute a high source of metalloproteinases (MMPs), and their interactions via P-selectin and P-selectin-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 three-fold 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.
Abou-Saleh
Haissam
H
Research Centre, Montreal Heart Institute and University of Montreal, Montreal, Quebec, Canada.
Théorêt
Jean-François
JF
Yacoub
Daniel
D
Merhi
Yahye
Y
D000906:Antibodies; D001792:Blood Platelets / Q000187:drug effects / Q000201:enzymology* / Q000276:immunology; D002448:Cell Adhesion; D002450:Cell Communication; D006801:Humans; D066298:In Vitro Techniques; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000276:immunology / Q000378:metabolism*; D009504:Neutrophils / Q000201:enzymology*; D019007:P-Selectin / Q000276:immunology / Q000378:metabolism*; D010973:Platelet Adhesiveness; D013917:Thrombin / Q000494:pharmacology
D000906:Antibodies; D008562:Membrane Glycoproteins; D019007:P-Selectin; C084882:P-selectin ligand protein; D013917:Thrombin; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9