Angiopoietin-1 Induces Migration of Monocytes in a Tie-2 and Integrin-Independent Manner
Angiopoietin-1 Induces Migration of Monocytes in a Tie-2 and Integrin-Independent Manner
复制标题
DOI：
10.1161/hypertensionaha.110.155556
复制
发表时间：
2010-09-01
期刊：
影响因子：
8.3
通讯作者：
Ahmed, Asif
中科院分区：
文献类型：
--
作者：
Ahmad, Shakil;Cudmore, Melissa J.;Ahmed, Asif
血管生成素-1（Angiopoietin-1，Ang-1）是一种血管生成因子，其激活Tie-2和整合素以促进血管壁重塑。最近发现的潜在促动脉粥样硬化的影响，血管紧张素-1促使我们调查是否血管紧张素-1促进单核细胞趋化性，内皮细胞结合，和跨内皮细胞迁移，动脉粥样硬化的进展中的关键事件。在这里，我们表明，血管紧张素-1诱导单核细胞的趋化性的方式是独立的Tie-2和整合素结合，但依赖于磷酸肌醇3-激酶和肝素。此外，血管紧张素-1促进磷酸肌醇3-激酶依赖性的单核细胞与内皮细胞单层的结合，并刺激跨内皮细胞迁移。体外活化细胞分选分析表明，外源性Ang-1可直接粘附于单核细胞和人脐静脉内皮细胞，但原代单核细胞不表达Tie-2 mRNA和蛋白。虽然Ang-1与人脐静脉内皮细胞的结合部分依赖于Tie-2和整合素，但Ang-1与单核细胞的结合不依赖于这些因素。最后，单核细胞与可溶性肝素预孵育废除了Ang-1与单核细胞的结合和迁移，并部分阻止了Ang-1与人脐内皮细胞的结合。总之，Ang-1诱导单核细胞趋化的机制依赖于磷酸肌醇3-激酶和肝素，但不依赖于Tie-2和整合素。Ang-1募集单核细胞的能力表明它可能在炎症性血管生成中起作用，并可能促进动脉粥样硬化。（高血压。2010;56：477-483）。
Angiopoietin-1 (Ang-1) is an angiogenic growth factor that activates Tie-2 and integrins to promote vessel wall remodeling. The recent finding of the potential proatherogenic effects of Ang-1 prompted us to investigate whether Ang-1 promotes monocyte chemotaxis, endothelial binding, and transendothelial migration, key events in the progression of atherosclerosis. Here, we show that Ang-1 induces chemotaxis of monocytes in a manner that is independent of Tie-2 and integrin binding but dependent on phosphoinositide 3-kinase and heparin. In addition, Ang-1 promoted phosphoinositide 3-kinase-dependent binding of monocytes to endothelial monolayers and stimulated transendothelial migration. Fluorescence-activated cell sorting analysis showed that exogenous Ang-1 adheres directly to monocytes as well as to human umbilical endothelial cells, but neither Tie-2 mRNA nor protein were expressed by primary monocytes. Although Ang-1 binding to human umbilical endothelial cells was partially Tie-2 and integrin dependent, Ang-1 binding to monocytes was independent of these factors. Finally, preincubation of monocytes with soluble heparin abrogated Ang-1 binding to monocytes and migration, and partially prevented Ang-1 binding to human umbilical endothelial cells. In summary, Ang-1 induces chemotaxis of monocytes by a mechanism that is dependent on phosphoinositide 3-kinase and heparin but independent of Tie-2 and integrins. The ability of Ang-1 to recruit monocytes suggests it may play a role in inflammatory angiogenesis and may promote atherosclerosis. (Hypertension. 2010;56:477-483.)