Integrin beta 1- and beta 3-mediated endothelial cell migration is triggered through distinct signaling mechanisms.
Integrin beta 1- and beta 3-mediated endothelial cell migration is triggered through distinct signaling mechanisms.
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DOI：
10.1083/jcb.121.1.163
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发表时间：
1993-04
期刊：
影响因子：
--
通讯作者：
Cheresh DA
中科院分区：
文献类型：
--
作者：
Leavesley DI;Schwartz MA;Rosenfeld M;Cheresh DA
人脐静脉内皮细胞在胶原蛋白和玻连蛋白上的附着、铺展和迁移分别由整合素α 2 β 1和α v β 3介导，并且这些事件在不存在细胞因子、生长因子或化学引诱物的情况下发生。细胞在这些配体上的附着和扩散发生在细胞外钙缺乏的情况下，胶原蛋白上的迁移也是如此。相反，玻连蛋白介导的迁移完全依赖于细胞外钙的存在。细胞与固定化玻连蛋白或抗α v β 3单抗的接触促进了[Ca 2 +]i的可测量的升高，这需要细胞外钙源，而胶原蛋白或抗α 2 β 1单抗不能促进这种信号传导事件。事实上，玻连蛋白介导的迁移和细胞内钙的升高显示出对细胞外钙的相同剂量依赖性。虽然玻连蛋白和胶原蛋白诱导钙内流的能力不同，但其各自整联蛋白的配体或抗体促进细胞内pH的等同增加，这与Na/H反向转运蛋白的激活一致，这是一个独立于细胞外钙的事件。这些结果支持两个突出的结论。首先，胶原蛋白和玻连蛋白通过其各自的整合素促进不同的细胞内信号传导事件。其次，α v β 3特异性钙内流不是细胞铺展所需的，但似乎促进了玻连蛋白上的细胞迁移。
Human umbilical vein endothelial cell attachment, spreading and migration on collagen and vitronectin are mediated by integrins alpha 2 beta 1 and alpha v beta 3, respectively, and these events take place in the absence of cytokines, growth factors, or chemoattractants. Cell attachment and spreading on these ligands occur in the absence of extracellular calcium, as does migration on collagen. In contrast, vitronectin-mediated migration is absolutely dependent on the presence of extracellular calcium. Cell contact with immobilized vitronectin or anti-alpha v beta 3 mAbs promotes a measurable rise in [Ca2+]i which requires an extracellular calcium source, whereas collagen, or anti- alpha 2 beta 1 mAbs fail to promote this signaling event. In fact, vitronectin-mediated migration and the rise in intracellular calcium showed the same dose dependence on extracellular calcium. While vitronectin and collagen differ in their ability to induce a calcium influx both ligands or antibodies to their respective integrins promote an equivalent increase in intracellular pH consistent with activation of the Na/H antiporter an event independent of extracellular calcium. These results support two salient conclusions. Firstly, collagen and vitronectin, through their respective integrins, promote distinct intracellular signaling events. Secondly, the alpha v beta 3 specific influx of calcium is not required for cell spreading yet appears to facilitate cellular migration on vitronectin.