Liu Yianzhu, Tejpal Neelam, You Junping, Li Xian C, Ghobrial Rafik M, Kloc Malgorzata
The Houston Methodist Hospital Research Institute, Central South University, Changsha 410008, Hunan, China; Department of Neurology, Xiangya Hospital, Central South University, Changsha 410008, Hunan, China.
The Houston Methodist Hospital Research Institute, Central South University, Changsha 410008, Hunan, China; The Department of Surgery, The Houston Methodist Hospital, Houston, TX, USA.
Cell Immunol. 2016 Feb;300:54-62. doi: 10.1016/j.cellimm.2015.12.005. Epub 2015 Dec 17.
Macrophages play an important role in immune responses including allograft rejection and they are one of the potential targets of anti-rejection therapies in organ transplantation. Macrophage alloreactivity relies on their phenotype/polarity, motility, phagocytosis and matrix degradation, which in turn depend on proper functioning of actin cytoskeleton and its regulators, the small GTPase RhoA and its downstream effector the Rho-associated protein kinase (ROCK). Several laboratories showed that administration of ROCK inhibitor Y-27632 to the graft recipient inhibits chronic rejection or rodent cardiac allografts. Here we studied the effect of Y-27632 on mouse peritoneal macrophage structure, polarity and functions in in vitro assays. We show that Y-27632 inhibitor affects macrophage phenotype/polarity, phagocytosis, migration, and matrix degradation. These novel findings suggest that the impediment of macrophage structure and function via interference with the RhoA/ROCK pathway has a potential to be therapeutically effective in organ transplantation.
巨噬细胞在包括同种异体移植排斥反应在内的免疫反应中发挥着重要作用，它们是器官移植抗排斥治疗的潜在靶点之一。巨噬细胞同种异体反应性依赖于其表型/极性、运动性、吞噬作用和基质降解，而这些又反过来依赖于肌动蛋白细胞骨架及其调节因子、小GTP酶RhoA及其下游效应物Rho相关蛋白激酶（ROCK）的正常功能。几个实验室表明，向移植受体施用ROCK抑制剂Y-27632可抑制慢性排斥反应或啮齿动物心脏同种异体移植。在这里，我们在体外实验中研究了Y-27632对小鼠腹腔巨噬细胞结构、极性和功能的影响。我们发现Y-27632抑制剂会影响巨噬细胞的表型/极性、吞噬作用、迁移和基质降解。这些新发现表明，通过干扰RhoA/ROCK途径来阻碍巨噬细胞的结构和功能在器官移植中具有潜在的治疗效果。
