Elongated Membrane Tethers, Individually Anchored by High Affinity α4β1/VCAM-1 Complexes, Are the Quantal Units of Monocyte Arrests
Elongated Membrane Tethers, Individually Anchored by High Affinity α4β1/VCAM-1 Complexes, Are the Quantal Units of Monocyte Arrests
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DOI：
10.1371/journal.pone.0064187
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发表时间：
2013-05-17
期刊：
影响因子：
3.7
通讯作者：
Moy, Vincent T.
中科院分区：
文献类型：
--
作者：
Chu, Calvin;Celik, Emrah;Moy, Vincent T.
α (4) β(1)整合素促进单核细胞滚动和粘附到血管内皮，并被单核细胞化学引诱蛋白（MCP-1）生理激活。本研究研究了THP-1细胞与固定化血管细胞粘附分子1 （VCAM-1）粘附的初始事件。通过AFM力测量，细胞粘附被证明是由两群α (4) β (1)/VCAM-1复合物介导的。低亲和力形式的α(4)和β(1)固定在细胞骨架的弹性元件上，而高亲和力的构象则耦合在细胞膜的粘性元件上。在接触100ms内，共固定MCP-1刺激的THP-1细胞对VCAM-1的粘附显著增加。细胞粘附增强伴随着细胞膜与细胞骨架的局部解耦和长膜系索的形成。锚索由多个α (4) β (1)/VCAM-1复合物单独锚定，延长了粘性锚索的延伸。在体内，这些膜系索的形成可能为阻止血管内滚动的单核细胞提供了量子结构单位。
The alpha(4)beta(1) integrin facilitates both monocyte rolling and adhesion to the vascular endothelium and is physiologically activated by monocyte chemoattractant protein (MCP-1). The current study investigated the initial events in the adhesion of THP-1 cells to immobilized Vascular Cell Adhesion Molecule 1 (VCAM-1). Using AFM force measurements, cell adhesion was shown to be mediated by two populations of alpha(4)beta(1)/VCAM-1 complexes. A low affinity form of alpha(4)beta(1) was anchored to the elastic elements of the cytoskeleton, while a higher affinity conformer was coupled to the viscous elements of the cell membrane. Within 100 ms of contact, THP-1 cells, stimulated by co-immobilized MCP-1, exhibited a tremendous increase in adhesion to VCAM-1. Enhanced cell adhesion was accompanied by a local decoupling of the cell membrane from the cytoskeleton and the formation of long membrane tethers. The tethers were individually anchored by multiple alpha(4)beta(1)/VCAM-1 complexes that prolonged the extension of the viscous tethers. In vivo, the formation of these membrane tethers may provide the quantal structural units for the arrest of rolling monocytes within the blood vessels.