RhoA activation promotes transendothelial migration of monocytes via ROCK
RhoA activation promotes transendothelial migration of monocytes via ROCK
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DOI：
10.1189/jlb.0203054
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发表时间：
2004-03-01
影响因子：
5.5
通讯作者：
de Vries, HE
中科院分区：
文献类型：
--
作者：
Honing, H;van den Berg, TK;de Vries, HE
单核细胞浸润到发炎的组织中需要细胞在内皮上的最初停滞，随后是牢固的粘附和随后的迁移。单核细胞和其他白细胞的迁移被认为涉及肌动蛋白细胞骨架的协调重塑。小GTP酶RhoA、Rac 1和Cdc 42是肌动蛋白重组的关键调节因子。在这项研究中，我们研究了Rho样GTP酶RhoA，Rac 1和Cdc 42的粘附和迁移的单核细胞通过脑内皮细胞表达其组成型活性或显性负结构在NR 8383大鼠单核细胞的作用。表达Cdc 42活性形式的单核细胞显示出减少的迁移，而Rac 1表达不影响粘附或迁移。相比之下，单核细胞中RhoA活性形式的表达导致其粘附和跨内皮细胞迁移的显著增加。发现RhoA的作用是由其下游效应物Rho激酶（ROCK）介导的，因为用选择性ROCK抑制剂Y-27632预处理阻止了这种增强的粘附和迁移。这些结果表明，单核细胞中的RhoA活化足以增强跨内皮细胞单层的粘附和迁移。
Monocyte infiltration into inflamed tissue requires the initial arrest of the cells on the endothelium followed by firm adhesion and their subsequent migration. Migration of monocytes and other leukocytes is believed to involve a coordinated remodeling of the actin cytoskeleton. The small GTPases RhoA, Rac1, and Cdc42 are critical regulators of actin reorganization. In this study, we have investigated the role of Rho-like GTPases RhoA, Rac1, and Cdc42 in the adhesion and migration of monocytes across brain endothelial cells by expressing their constitutively active or dominant-negative constructs in NR8383 rat monocytic cells. Monocytes expressing the active form of Cdc42 show a reduced migration, whereas Rac1 expression did not affect adhesion or migration. In contrast, expression of the active form of RhoA in monocytes leads to a dramatic increase in their adhesion and migration across endothelial cells. The effect of RhoA was found to be mediated by its down-stream effector Rho kinase (ROCK), as pretreatment with the selective ROCK inhibitor Y-27632 prevented this enhanced adhesion and migration. These results demonstrate that RhoA activation in monocytes is sufficient to enhance adhesion and migration across monolayers of endothelial cells.