Neutrophil P-selectin-glycoprotein-ligand-binding to platelet P-selectin enhances metalloproteinase 2 secretion and platelet-neutrophil aggregation
Neutrophil P-selectin-glycoprotein-ligand-binding to platelet P-selectin enhances metalloproteinase 2 secretion and platelet-neutrophil aggregation
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DOI：
10.1160/th05-05-0344
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发表时间：
2005-12-01
影响因子：
6.7
通讯作者：
Merhi, Y
中科院分区：
文献类型：
--
作者：
Abou-Saleh, H;Théorêt, JFO;Merhi, Y
血小板和中性粒细胞是金属蛋白酶(MMPs)的重要来源，它们通过P-选择素和P-选择素-糖蛋白-配体-1(PSGL-1)相互作用参与血栓形成、血管重塑和再狭窄。我们研究了这些相互作用对血小板和中性粒细胞聚集的基质金属蛋白酶-2的分泌和功能的影响。凝血酶激活后，人血小板分泌基质金属蛋白酶-2的能力显著增加三倍，在中性粒细胞存在的情况下则增加一倍。中性粒细胞培养上清液对血小板分泌基质金属蛋白酶-2无影响，中性粒细胞分泌大量基质金属蛋白酶-9，在凝血酶激活或有血小板存在的情况下保持不变。血小板P-选择素在激活后显著增加，触发了血小板与中性粒细胞的结合，这一结合可被P-选择素或PSGL-1拮抗剂完全抑制，而被GPIIb/IIIa拮抗剂则减少50%。P-选择素或PSGL-1拮抗剂可抑制中性粒细胞刺激的血小板分泌基质金属蛋白酶-2，减少血小板-中性粒细胞聚集。P-选择素和PSGL-1通过P-选择素和PSGL-1之间的黏附相互作用，促进了血小板与中性粒细胞的聚集，从而促进了血小板的活化和与中性粒细胞的结合，从而促进了血小板的分泌。
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 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.