Shimizu Koichi, Mitchell Richard N
Department of Pathology, Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
Arterioscler Thromb Vasc Biol. 2008 Nov;28(11):1937-49. doi: 10.1161/ATVBAHA.107.161232. Epub 2008 Sep 18.
Despite the development of effective immunosuppressive therapy, transplant graft arterial disease (GAD) remains the major limitation to long-term graft survival. Multiple immune and nonimmune risk factors contribute to this vasculopathic intimal hyperplastic process. Thus, initial interplay between host inflammatory cells and donor endothelial cells triggers alloimmune responses, whereas alloantigen-independent factors such as prolonged ischemia, surgical manipulation, ischemia-reperfusion injury, and hyperlipidemia enhance the antigen-dependent events. Intrinsic to all stages of this process are chemokines, a family of 8- to 10-kDa proteins mediating directional migration of immune cells to sites of inflammation and injury. Beyond their role in immune-cell chemotaxis, chemokines also contribute to cellular activation, vascular remodeling, and angiogenesis. Expression of chemokines and their cognate receptors in allografts correlates with acute organ rejection, as well as GAD. Moreover, chemokine or chemokine receptor blockade prolongs graft survival and attenuates GAD in experimental models. Further studies will likely confirm a substantial utility for antichemokine therapy in human organ transplantation.
尽管有效的免疫抑制疗法有所发展，但移植血管疾病（GAD）仍然是长期移植物存活的主要限制因素。多种免疫和非免疫风险因素促成了这种血管病变性内膜增生过程。因此，宿主炎症细胞与供体内皮细胞之间的初始相互作用引发同种免疫反应，而诸如长时间缺血、手术操作、缺血再灌注损伤和高脂血症等非抗原依赖性因素则增强了抗原依赖性事件。趋化因子是这个过程所有阶段的内在因素，它是一族8至10千道尔顿的蛋白质，介导免疫细胞向炎症和损伤部位的定向迁移。除了在免疫细胞趋化作用中的作用外，趋化因子还促进细胞活化、血管重塑和血管生成。同种异体移植物中趋化因子及其同源受体的表达与急性器官排斥以及GAD相关。此外，在实验模型中，趋化因子或趋化因子受体阻断可延长移植物存活并减轻GAD。进一步的研究可能会证实抗趋化因子疗法在人类器官移植中的巨大效用。
