Department of Plasma Proteins, Molecular Cell Biology Lab, Sanquin Research and Landsteiner Laboratory, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
Department of Central Facility, Sanquin Research and Landsteiner Laboratory, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
Small GTPases. 2020 May;11(3):225-232. doi: 10.1080/21541248.2017.1377815. Epub 2018 Jan 29.
Active remodeling of the actin cytoskeleton in endothelial cells is necessary for allowing leukocytes to cross the barrier during the process of transendothelial migration (TEM). Involvement of RhoGTPases to regulate actin organization is inevitable, and we recently reported on the local function of RhoA in limiting vascular leakage during leukocyte TEM. As a follow-up we investigated here the possible involvement of two other closely-related GTPases; RhoB and RhoC, in regulating leukocyte TEM and vascular barrier maintenance. Physiological flow experiments showed no substantial involvement of either endothelial RhoB or RhoC in neutrophil adhesion and transmigration efficiency. Besides neutrophil TEM, we did not observe a role for endothelial RhoB or RhoC in limiting vascular leakage in both inflammatory conditions and during TEM. In conclusion, endothelial RhoB and RhoC are both dispensable for regulating leukocyte diapedesis and for maintaining vascular barrier function under inflammatory conditions and during leukocyte diapedesis.
内皮细胞中肌动蛋白细胞骨架的活跃重塑对于允许白细胞在穿越内皮细胞迁移（TEM）过程中穿过屏障是必要的。RhoGTPases 参与调节肌动蛋白组织是不可避免的，我们最近报道了 RhoA 在限制白细胞 TEM 期间血管渗漏中的局部功能。作为后续研究，我们在此调查了另外两种密切相关的 GTPases；RhoB 和 RhoC 在调节白细胞 TEM 和血管屏障维持中的可能作用。生理流动实验表明，内皮细胞 RhoB 或 RhoC 均未实质性参与中性粒细胞的黏附和迁移效率。除了中性粒细胞 TEM 之外，我们在炎症条件下和 TEM 期间均未观察到内皮细胞 RhoB 或 RhoC 对限制血管渗漏有作用。总之，内皮细胞 RhoB 和 RhoC 对于调节白细胞穿胞作用和在炎症条件下以及白细胞穿胞作用期间维持血管屏障功能都是可有可无的。
