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首页> 外文期刊>Journal of Leukocyte Biology: An Official Publication of the Reticuloendothelial Society >RhoA activation promotes transendothelial migration of monocytes via ROCK.
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RhoA activation promotes transendothelial migration of monocytes via ROCK.

机译：RhoA激活通过ROCK促进单核细胞的跨内皮迁移。

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摘要

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.
机译：单核细胞浸润到发炎的组织中需要先将细胞停滞在内皮细胞上，然后牢固粘附并随后迁移。据认为单核细胞和其他白细胞的迁移涉及肌动蛋白细胞骨架的协调重塑。小型GTPases RhoA，Rac1和Cdc42是肌动蛋白重组的关键调节剂。在这项研究中，我们通过在NR8383大鼠单核细胞中表达组成型活性或显性阴性构建体，研究了Rho样GTPases RhoA，Rac1和Cdc42在单核细胞跨脑内皮细胞的粘附和迁移中的作用。表达Cdc42活性形式的单核细胞显示出减少的迁移，而Rac1表达不影响粘附或迁移。相反，RhoA活性形式在单核细胞中的表达导致其粘附力和跨内皮细胞迁移的急剧增加。发现RhoA的作用是由其下游效应器Rho激酶（ROCK）介导的，因为用选择性ROCK抑制剂Y-27632进行的预处理可以防止这种增强的粘附和迁移。这些结果表明，单核细胞中的RhoA激活足以增强粘附和跨内皮细胞单层迁移。

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