P-selectin glycoprotein ligand 1 and β2-integrins cooperate in the adhesion of leukocytes to von Willebrand factor
P-selectin glycoprotein ligand 1 and β2-integrins cooperate in the adhesion of leukocytes to von Willebrand factor
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DOI：
10.1182/blood-2006-03-010322
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发表时间：
2006-12-01
期刊：
影响因子：
20.3
通讯作者：
Denis, Cecile V.
中科院分区：
文献类型：
--
作者：
Pendu, Ronan;Terraube, Virginie;Denis, Cecile V.
血管性血友病因子(VWF)是止血的重要成分。然而，使用VWF缺陷小鼠进行的动物研究表明，VWF也可能导致炎症。在目前的研究中，我们证明了VWF能够在静态和流动条件下与多形核白细胞(PMN)和单核细胞相互作用。流动状态下的黏附以与静止PMN的短暂接触为主，而佛波醇-12-肉豆蔻酸酯-13-醋酸酯(PMA)刺激的PMN黏附以牢固黏附为主。PMN与VWF的瞬时结合似乎是由β-选择素糖蛋白配体-1(PSGL-1)介导的。此外，重组PSGL-1蛋白和细胞表面表达的PSGL-1直接与VWF相互作用。对于PMA刺激的PMN的稳定黏附，我们观察到β2-整合素功能的抑制剂中性粒细胞抑制因子对静态黏附和流动黏附有强烈的抑制作用(大于75%)。此外，分离的αMβ2的I结构域与VWF结合，表达αLβ2或αXβ2的细胞株能有效地与VWF结合。综上所述，我们的数据显示，VWF可以作为各种白细胞亚群(单核细胞，PMN)的粘附面。与VWF-血小板相互作用类似，VWF为参与滚动(PSGL-1)和稳定(β2-整合素)黏附的白细胞受体提供结合部位。VWF的独特之处在于它在与白细胞的相互作用中结合了滚动和稳定黏附步骤的内在能力。
Von Willebrand factor (VWF) is an essential component of hemostasis. However, animal studies using VWF-deficient mice suggest that VWF may also contribute to inflammation. In the present study, we demonstrate that VWF was able to interact with polymorphonuclear leukocytes (PMNs) and monocytes under static and flow conditions. Adhesion under flow was dominated by short-lasting contact with resting PMNs, whereas adhesion of phorbol-12-myristate-13-acetate (PMA)stimulated PMNs was characterized by firm adhesion. Transient binding of PMNs to VWF appeared to be mediated by beta-selectin glycoprotein ligand-1 (PSGL-1). Moreover, recombinant PSGL-1 protein and cell surf ace-expressed PSGL-1 directly interacted with VWF. As for stable adhesion by PMA-stimulated PMNs, we observed that static adhesion and adhesion under flow were strongly inhibited (greater than 75%) by neutrophil-inhibitory factor, an inhibitor of beta 2-integrin function. In addition, the isolated I-domain of alpha M beta 2 bound to VWF, and cell lines expressing alpha L beta 2 or alpha X beta 2 adhered efficiently to VWF. Taken together, our data showed that VWF can function as an adhesive surface for various leukocyte subsets (monocytes, PMNs). Analogous to VWF-platelet interaction, VWF provided binding sites for leukocyte receptors involved in rolling (PSGL-1) and stable (beta 2-integrins) adhesion. VWF is unique in its intrinsic capacity to combine the rolling and the stable adhesion step in the interaction with leukocytes.