RGD-dependent vacuolation and lumen formation observed during endothelial cell morphogenesis in three-dimensional fibrin matrices involves the αvβ3 and α5β1 integrins
RGD-dependent vacuolation and lumen formation observed during endothelial cell morphogenesis in three-dimensional fibrin matrices involves the αvβ3 and α5β1 integrins
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DOI：
10.1016/s0002-9440(10)65038-9
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发表时间：
2000-05-01
影响因子：
6
通讯作者：
Davis, GE
中科院分区：
文献类型：
--
作者：
Bayless, KJ;Salazar, R;Davis, GE
最近的数据揭示了α(v)β(3)整合素参与血管生成。然而，迄今为止，很少有研究表明该受体在内皮细胞形态发生的体外测定中具有令人信服的作用，其中可以检查确定的步骤。在这里，我们提供的数据显示，两种整合素α(v)β(3)和α(5)β(1)调节三维纤维蛋白基质中的人内皮细胞空泡化和管腔形成。重新悬浮在纤维蛋白中的细胞形成细胞内液泡，这些液泡合并成腔结构。同时添加抗α(v)β(3)和抗α(5)整联蛋白抗体完全抑制了这些形态发生事件。环Arg-Gly-Asp (cRGD) 肽和抗α(5) 整联蛋白抗体的组合也可实现完全阻断。单独使用对照Arg-Gly-Glu (RGE)肽或与对照抗体组合没有观察到阻断。最后，我们能够证明在添加 cRGD 肽与抗 α(5) 整联蛋白抗体几个小时后，液泡和管腔消退。单独使用对照肽或与对照抗体组合时没有观察到这些效应。我们在这里报道了α(v)β(3)和α(5)β(1)整合素新参与纤维蛋白基质中的空泡形成和管腔形成，暗示多个整合素在内皮细胞形态发生中的作用。
Recent data have revealed the involvement of the alpha(v)beta(3) integrin in angiogenesis. However, few studies to date have provided, a convincing role for this receptor in in vitro assays of endothelial cell morphogenesis where defined steps can be examined. Here, we present data showing that two integrins, alpha(v)beta(3) and alpha(5)beta(1), regulate human endothelial cell vacuolation and lumen formation in three-dimensional fibrin matrices. Cells resuspended in fibrin formed intracellular vacuoles that coalesced into lumenal structures. These morphogenic events were completely inhibited by the simultaneous addition of anti-alpha(v)beta(3) and anti-alpha(5) integrin antibodies. Complete blockade was also accomplished with a combination of the cyclic Arg-Gly-Asp (cRGD) peptide and anti-alpha(5) integrin antibodies. No blockade was observed with the control Arg-Gly-Glu (RGE) peptide alone or in combination with control antibodies. Finally, we were able to demonstrate regression of vacuoles and lumens several hours after the addition of cRGD peptides combined with anti-alpha(5) integrin antibodies. These effects were not observed with control peptides alone or in combination with control antibodies. We report here the novel involvement of both the alpha(v)beta(3) and alpha(5)beta(1) integrins in vacuolation and lumen formation in a fibrin matrix, implicating a role for multiple integrins in endothelial cell morphogenesis.