VLA-4 integrin mediates lymphocyte migration on the inducible endothelial cell ligand VCAM-1 and the extracellular matrix ligand fibronectin.
VLA-4 integrin mediates lymphocyte migration on the inducible endothelial cell ligand VCAM-1 and the extracellular matrix ligand fibronectin.
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DOI：
10.1016/s0021-9258(19)74516-5
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发表时间：
1993-11
期刊：
影响因子：
--
通讯作者：
Po-Ying Chan;A. Aruffo
中科院分区：
文献类型：
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作者：
Po-Ying Chan;A. Aruffo
我们在此测试了淋巴细胞在粘附其细胞因子诱导的内皮细胞配体VCAM-1或其细胞外基质配体纤维连接蛋白时利用β 1整合素vcam -4介导细胞迁移的能力。我们使用了一种体外系统，该系统由纯化的VCAM-1/Fc融合蛋白或纤维连接蛋白固定在多孔聚碳酸酯膜上，以定量测量Epstein-Barr病毒转化的B细胞系（SLA）和来自正常供体的T淋巴细胞的迁移效率。我们发现SLA细胞和T淋巴母细胞都以位点密度依赖的方式迁移穿过涂有VCAM-1/Fc或纤维连接蛋白的膜。在VCAM-1/Fc或纤维连接蛋白的最佳位点密度以上和以下，迁移效率下降。通过VCAM-1/Fc包被膜的淋巴细胞迁移的数量是纤维连接蛋白包被膜的6-20倍。当配体固定在塑料上时，与纤维连接蛋白相比，VCAM-1/Fc具有更高的粘附淋巴细胞数量和更高的粘附度，这一差异迁移效率与细胞的激活状态无关。这些结果表明了细胞粘附强度对迁移反应的严格调控，以及细胞在粘附基质上的固定和迁移行为之间的微妙平衡。与β 2整合素LFA-1一样，vca -4可能是一种动力粘附受体，通过与VCAM-1和纤维连接蛋白结合参与淋巴细胞的跨内皮迁移和淋巴细胞向淋巴组织或外周组织的浸润。
We herein tested the ability of lymphocytes to utilize the beta 1 integrin VLA-4 to mediate cell migration when adhering to its cytokine-inducible endothelial cell ligand VCAM-1 or its extracellular matrix ligand fibronectin. We used an in vitro system consisting of purified VCAM-1/Fc fusion protein or fibronectin immobilized on porous polycarbonate membranes to quantitatively measure the migration efficiency of an Epstein-Barr virus-transformed B cell line (SLA) and T lymphoblasts derived from normal donors. We found that both SLA cells and T lymphoblasts migrated across membranes coated with VCAM-1/Fc or fibronectin in a site density-dependent manner. Above and below an optimal site density of VCAM-1/Fc or fibronectin, the migration efficiency decreased. A 6-20-fold higher number of lymphocytes migrated across membranes coated with VCAM-1/Fc than with fibronectin. The differential migration efficiency is consistent with a higher number of adherent lymphocytes and a higher avidity of adhesion for VCAM-1/Fc than for fibronectin when the ligands were immobilized on plastic, and is independent of the activation state of the cells. These results demonstrated a stringent regulation of migratory response by cell adhesion strength and a delicate balance between stationary and migratory behaviors of a cell on the adhesive substrates. Like the beta 2 integrin LFA-1, VLA-4 may be a locomotive adhesion receptor which is involved in the transendothelial migration of lymphocytes and the infiltration of lymphocytes into lymphoid or peripheral tissues by binding to VCAM-1 and fibronectin.