CX3CR1 and Vascular Adhesion Protein-1-Dependent Recruitment of CD16+ Monocytes Across Human Liver Sinusoidal Endothelium
CX3CR1 and Vascular Adhesion Protein-1-Dependent Recruitment of CD16+ Monocytes Across Human Liver Sinusoidal Endothelium
复制标题
DOI：
10.1002/hep.23591
复制
发表时间：
2010-06-01
期刊：
影响因子：
13.5
通讯作者：
Adams, David H.
中科院分区：
文献类型：
--
作者：
Aspinall, Alexander I.;Curbishley, Stuart M.;Adams, David H.
肝脏含有巨噬细胞和髓系树突状细胞(MDCs)，它们对肝脏炎症的调节至关重要。大多数肝巨噬细胞和巨噬细胞是通过与肝窦内皮细胞(HSECs)相互作用而从血液中募集的单核细胞。人CD16(+)单核细胞被认为含有组织巨噬细胞和MDCs的前体细胞群。我们报道在慢性炎症性肝病中，CD16(+)细胞定位于炎症和纤维化活跃的区域，细胞表面受体的独特组合促进了CD16(+)单核细胞在生理流动下通过人HSEC的跨内皮迁移。Cx(3)CR1激活是控制血流下跨内皮细胞迁移的主要百日咳敏感机制，慢性炎症性肝病患者肝窦表面Cx(3)CR1配体Cx(3)CL1表达增加。CD16(+)单核细胞暴露于固定化纯化的CX(3)CL1可触发β1整合素介导的与血管细胞黏附分子-1的黏附，并诱导其形成迁移表型。CD16(+)单核细胞在移行或暴露于可溶性Cx(3)Cl1后，Cx(3)CR1的表达迅速消失。血流作用下HSECs间的黏附和迁移也依赖于HSECs上的血管黏附蛋白-1(VAP-1)。结论：CD16(+)单核细胞是通过YAP-1和CX(3)CR1介导的整合素活化的黏附信号联合募集的。因此，一种新的表面分子组合，包括VAP-1和CX(3)CL1，促进CD16(+)单核细胞募集到肝脏，使它们定位于慢性炎症和纤维化部位。(《肝病》2010；51：2030-2039)
The liver contains macrophages and myeloid dendritic cells (mDCs) that are critical for the regulation of hepatic inflammation. Most hepatic macrophages and mDCs are derived from monocytes recruited from the blood through poorly understood interactions with hepatic sinusoidal endothelial cells (HSECs). Human CD16(+) monocytes are thought to contain the precursor populations for tissue macrophages and mDCs. We report that CD16(+) cells localize to areas of active inflammation and fibrosis in chronic inflammatory liver disease and that a unique combination of cell surface receptors promotes the transendothelial migration of CD16(+) monocytes through human HSECs under physiological flow. CX(3)CR1 activation was the dominant pertussis-sensitive mechanism controlling transendothelial migration under flow, and expression of the CX(3)CR1 ligand CX(3)CL1 is increased on hepatic sinusoids in chronic inflammatory liver disease. Exposure of CD16(+) monocytes to immobilized purified CX(3)CL1 triggered beta 1-integrin-mediated adhesion to vascular cell adhesion molecule-1 and induced the development of a migratory phenotype. Following transmigration or exposure to soluble CX(3)CL1, CD16(+) monocytes rapidly but transiently lost expression of CX(3)CR1. Adhesion and transmigration across HSECs under flow was also dependent on vascular adhesion protein-1 (VAP-1) on the HSECs. Conclusion: Our data suggest that CD16(+) monocytes are recruited by a combination of adhesive signals involving YAP-1 and CX(3)CR1 mediated integrin-activation. Thus a novel combination of surface molecules, including VAP-1 and CX(3)CL1 promotes the recruitment of CD16(+) monocytes to the liver, allowing them to localize at sites of chronic inflammation and fibrosis. (HEPATOLOGY 2010;51:2030-2039)