Dejana E, Languino L R, Colella S, Corbascio G C, Plow E, Ginsberg M, Marchisio P C
Istituto di Ricerche Farmacologiche Mario Negri, Milano, Italy.
Blood. 1988 Mar;71(3):566-72.
Previous studies have shown that human endothelial cells (ECs) adhere to fibrinogen (fg) and fibronectin (fn) and organize their cytoskeleton on these substrata. However, the mechanism governing this chain of events is poorly known. In ECs glycoproteins immunologically and biochemically similar to the platelet membrane GpIIb-IIIa complex have been described. The functional role of this complex in ECs remains to be established. In this study we show that the antigens recognized by polyclonal antibodies raised against human platelet GpIIb-IIIa and crossreacting with the EC form have a discrete and well-organized distribution at cell adhesion structures. Indeed these antigens are located at vinculin-rich focal contacts found at the membrane insertion of microfilament bundles of the stress fiber type. They are also found at cell-to-cell contacts and, with a diffuse pattern, at the dorsal surface of ECs. GpIIb-IIIa antibodies, added to EC suspensions prior to plating, inhibit EC spreading on fg and vitronectin (vn) substrata in a concentration-dependent way. In contrast, the antibodies are very poorly active when the cells are seeded on fn-coated glass. The same antibodies, added to adherent cells, disrupt cell-to-cell contacts and cause their rounding and detachment. Overall these results indicate that EC GpIIb-IIIa complex is involved in controlling the adhesion mechanism of these cells to extracellular matrix proteins.
先前的研究表明,人内皮细胞(ECs)可黏附于纤维蛋白原(fg)和纤连蛋白(fn),并在这些底物上组织其细胞骨架。然而,支配这一系列事件的机制却鲜为人知。在ECs中,已描述了在免疫学和生物化学上与血小板膜糖蛋白IIb-IIIa复合物相似的糖蛋白。该复合物在ECs中的功能作用仍有待确定。在本研究中,我们表明,针对人血小板糖蛋白IIb-IIIa产生的多克隆抗体所识别的、与EC形式发生交叉反应的抗原,在细胞黏附结构处具有离散且组织良好的分布。实际上,这些抗原位于富含纽蛋白的黏着斑处,这些黏着斑位于应力纤维类型的微丝束的膜插入处。它们也存在于细胞间接触处,并以弥散模式存在于ECs的背表面。在接种前添加到EC悬浮液中的糖蛋白IIb-IIIa抗体,以浓度依赖的方式抑制EC在fg和玻连蛋白(vn)底物上的铺展。相反,当细胞接种在fn包被的玻璃上时,这些抗体的活性非常低。添加到贴壁细胞中的相同抗体,会破坏细胞间接触并导致细胞变圆和脱离。总体而言,这些结果表明,EC糖蛋白IIb-IIIa复合物参与控制这些细胞与细胞外基质蛋白的黏附机制。