Roles of α4 integrins/VCAM-1 and LFA-1/ICAM-1 in the binding and transendothelial migration of T lymphocytes and T lymphoblasts across high endothelial venules
Roles of α4 integrins/VCAM-1 and LFA-1/ICAM-1 in the binding and transendothelial migration of T lymphocytes and T lymphoblasts across high endothelial venules
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DOI：
10.1093/intimm/12.3.241
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发表时间：
2000-03-01
影响因子：
4.4
通讯作者：
Ager, A
中科院分区：
文献类型：
--
作者：
Faveeuw, C;Di Mauro, ME;Ager, A
已经确定了几种介导淋巴细胞与流动血液中的高内皮微静脉（HEV）结合的细胞粘附分子，但淋巴细胞穿过HEV壁迁移到淋巴结（LN）的调节还远未了解。在本研究中，我们使用了淋巴细胞跨HEV迁移的体外模型，并分析了两种整合素在T淋巴细胞和T淋巴母细胞的结合和跨内皮迁移中的作用，T淋巴细胞与培养的大鼠LN HEV高内皮细胞（HEC）的粘附不同于T淋巴母细胞，因为粘附和迁移的T淋巴母细胞的百分比较高，而IFN-γ不增加粘附和迁移。HEC的γ预处理。α 4整联蛋白、VCAM-1或LFA-1的抗体最大程度地抑制T淋巴细胞粘附40- 50%，而ICAM-1的抗体效果较差（90%抑制）。在LFA-1抗体存在下粘附的T淋巴细胞显示出降低的迁移水平，而在α（4）整联蛋白抗体存在下，迁移略有增加。α 4整联蛋白、VCAM-1、LFA-1或ICAM-1的抗体对T淋巴母细胞粘附几乎没有影响（最大抑制10-30%），并且在α（4）整联蛋白或LFA-1抗体存在下T淋巴母细胞正常迁移。然而，α（4）整联蛋白和LFA-1抗体对T淋巴母细胞粘附的作用是协同的，给出>90%的粘附抑制。这些结果表明，大多数T淋巴母细胞使用α（4）整合素或LFA-1结合和迁移HEV，这些整合素对活化的T细胞的作用是重叠和冗余的。相反，整合素支持未活化的T淋巴细胞与HEV表面的半最大结合，并且LFA-1比α（4）整合素对跨内皮迁移的贡献更大。
Several cell adhesion molecules that mediate the binding of lymphocytes to high endothelial venules (HEV) from flowing blood have been identified but the regulation of lymphocyte migration across the HEV wall into the lymph node (LN) is far from understood. In this study we have used an in vitro model of lymphocyte migration across HEV, and analysed the roles of two integrins in the binding and transendothelial migration of T lymphocytes and T lymphoblasts, The adhesion of T lymphocytes to high endothelial cells (HEC) cultured from rat LN HEV differed from that of T lymphoblasts since the percentage of T lymphoblasts that adhered and transmigrated was higher and was not increased by IFN-gamma pretreatment of HEC. Antibodies to alpha(4) integrins, VCAM-1 or LFA-1 maximally inhibited T lymphocyte adhesion by 40-50%, whereas antibodies to ICAM-1 were less effective (90% inhibition. T lymphocytes which adhered in the presence of LFA-1 antibody showed reduced levels of transmigration and, in the presence of alpha(4) integrin antibody, slightly increased transmigration. Antibodies to a4 integrins, VCAM-1, LFA-1 or ICAM-1 had little effect on T lymphoblast adhesion (maxima of 10-30% inhibition) and T lymphoblasts transmigrated normally in the presence of either alpha(4) integrin or LFA-1 antibodies. However, the effects of alpha(4) integrin and LFA-1 antibodies on T lymphoblast adhesion were synergistic, giving >90% inhibition of adhesion. These results suggest that the majority of T lymphoblasts use either alpha(4) integrins or LFA-1 to bind and transmigrate HEV, and the roles of these integrins on activated T cells are overlapping and redundant. In contrast, either integrin supports half-maximal binding of unactivated T lymphocytes to the surface of HEV and LFA-1 makes a larger contribution than alpha(4) integrins to transendothelial migration.