Intercellular adhesion molecule-1 (ICAM-1) regulates endothelial cell motility through a nitric oxide-dependent pathway
Intercellular adhesion molecule-1 (ICAM-1) regulates endothelial cell motility through a nitric oxide-dependent pathway
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DOI：
10.1074/jbc.m312025200
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发表时间：
2004-04-30
影响因子：
4.8
通讯作者：
Bullard, DC
中科院分区：
文献类型：
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作者：
Kevil, CG;Orr, AW;Bullard, DC
内皮细胞迁移的协调调节是血管生成过程中不可或缺的一个过程。然而，调节内皮细胞迁移的分子机制在很大程度上仍然未知。细胞粘附分子的表达增加与血管生成有关，但这些分子的确切作用尚不清楚。在这里，我们检验了细胞间粘附分子-1 （ICAM-1）对内皮细胞迁移很重要的假设。在缺乏icam -1的内皮细胞中，细胞总位移和定向迁移明显减弱。对icam -1缺陷细胞的进一步检查显示，与野生型内皮相比，Akt - Thr（308）和内皮一氧化氮合酶丝氨酸（1177）磷酸化和NO生物利用度降低，肌动蛋白应激纤维形成增加，并且缺乏明显的细胞极性。将ICAM-1突变细胞与NO供体DETA NONOate （0.1 muM）一起补充，可以纠正迁移缺陷，减少应激纤维的形成，并增强假足和尾足的形成。这些数据表明，ICAM-1通过调节内皮一氧化氮合酶的激活和肌动蛋白细胞骨架的组织，促进细胞极性的发展，调节内皮细胞的迁移。
Coordinated regulation of endothelial cell migration is an integral process during angiogenesis. However, molecular mechanisms regulating endothelial cell migration remain largely unknown. Increased expression of cell adhesion molecules has been implicated during angiogenesis, yet the precise role of these molecules is unclear. Here, we examined the hypothesis that intercellular adhesion molecule-1 (ICAM-1) is important for endothelial cell migration. Total cell displacement and directional migration were significantly attenuated in ICAM-1-deficient endothelium. Closer examination of ICAM-1-deficient cells revealed decreased Akt Thr(308) and endothelial nitric-oxide synthase Ser(1177) phosphorylation and NO bioavailability, increased actin stress fiber formation, and a lack of distinct cell polarity compared with wild-type endothelium. Supplementation of ICAM-1 mutant cells with the NO donor DETA NONOate (0.1 muM) corrected the migration defect, diminished stress fiber formation, and enhanced pseudopod and uropod formation. These data demonstrate that ICAM-1 facilitates the development of cell polarity and modulates endothelial cell migration through a pathway regulating endothelial nitric-oxide synthase activation and organization of the actin cytoskeleton.