Platelet binding to monocytes increases the adhesive properties of monocytes by up-regulating the expression and functionality of β1 and B2 integrins
Platelet binding to monocytes increases the adhesive properties of monocytes by up-regulating the expression and functionality of β1 and B2 integrins
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DOI：
10.1189/jlb.0605318
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发表时间：
2006-03-01
影响因子：
5.5
通讯作者：
Zwaginga, Jaap J.
中科院分区：
文献类型：
--
作者：
Martins, Paula A. da Costa;van Gils, Janine M.;Zwaginga, Jaap J.
人单核细胞粘附于活化的血小板，导致血小板-单核细胞复合物（PMC）的形成。复合物的形成依赖于血小板展示的P-选择素与白细胞上P-选择素的特异性配体P-选择素糖蛋白配体-1（PSGL-1）之间的相互作用。我们最近发现，PMC内的单核细胞对活化的内皮细胞的粘附能力增强。为了更好地理解血小板结合对单核细胞粘附于活化内皮的能力的影响，研究了P-选择素-PSGL-1相互作用诱导的整合素功能的变化。血小板与单核细胞通过P选择素-PSGL-1相互作用的结合显示出增加α（4）β（1）和α（M）β 2整联蛋白的表达和活性，伴随着L-选择素表达的降低。此外，血小板与单核细胞的结合导致单核细胞与细胞间粘附分子-1、血管细胞粘附分子-1和纤连蛋白的粘附增加。血小板结合也是单核细胞跨内皮迁移增加的原因。在PSGL-1与特异性抗体或P-选择素免疫球蛋白结合后观察到类似的效果。我们的数据表明，血小板通过P-选择素与单核细胞上的PSGL-1结合，诱导β（1）和β（2）整合素的上调和活化，并增加单核细胞与活化内皮细胞的粘附。因此，PMC内的单核细胞处于较高的活化状态，因此可能具有增加的致动脉粥样硬化能力。
Human monocytes adhere to activated platelets, resulting in the formation of platelet-monocyte complexes (PMC). Complex formation depends on the interaction between platelet-displayed P-selectin and the specific ligand for P-selectin on leukocytes, P-selectin glycoprotein ligand-1 (PSGL-1). We have recently shown that monocytes within PMC have increased adhesive capacity to the activated endothelium. To better understand the effect of platelet binding on the capacity of monocytes to adhere to activated endothelium, the P-selectin-PSGL-1 interaction-induced changes in integrin functionality were studied. The binding of platelets to monocytes via Pselectin-PSGL-1 interactions was shown to increase expression and activity of alpha(4)beta(1) and alpha(M)beta 2 integrin, with a concomitant decrease in L-selectin expression. Furthermore, the binding of platelets to monocytes resulted in increased monocyte adhesion to intercellular adhesion molecule-1, vascular cell adhesion molecule-1, and fibronectin. Platelet binding was also responsible for an increase in monocyte transendothelial migration. Similar effects were observed after engagement of PSGL-1 with specific antibodies or with P-selectin immunoglobulin protein. Our data suggest that platelets, by binding via P-selectin to PSGL-1 on monocytes, induce up-regulation and activation of beta(1) and beta(2) integrins and increased adhesion of monocytes to activated endothelium. Hence, monocytes within PMC are in a higher state of activation and may have, therefore, an increased atherogenic capacity.