Department of Immunobiology, Yale School of Medicine, New Haven, CT.
Am J Transplant. 2015 Jul;15(7):1748-54. doi: 10.1111/ajt.13242. Epub 2015 Mar 23.
Human vascularized allografts are perfused through blood vessels composed of cells (endothelium, pericytes, and smooth muscle cells) that remain largely of graft origin and are thus subject to host alloimmune responses. Graft vessels must be healthy to maintain homeostatic functions including control of perfusion, maintenance of permselectivity, prevention of thrombosis, and participation in immune surveillance. Vascular cell injury can cause dysfunction that interferes with these processes. Graft vascular cells can be activated by mediators of innate and adaptive immunity to participate in graft inflammation contributing to both ischemia/reperfusion injury and allograft rejection. Different forms of rejection may affect graft vessels in different ways, ranging from thrombosis and neutrophilic inflammation in hyperacute rejection, to endothelialitis/intimal arteritis and fibrinoid necrosis in acute cell-mediated or antibody-mediated rejection, respectively, and to diffuse luminal stenosis in chronic rejection. While some current therapies targeting the host immune system do affect graft vascular cells, direct targeting of the graft vasculature may create new opportunities for preventing allograft injury and loss.
同种异体血管移植物通过由细胞（内皮细胞、周细胞和平滑肌细胞）组成的血管进行灌注，这些细胞在很大程度上仍然来自移植物，因此容易受到宿主同种免疫反应的影响。移植物血管必须保持健康，以维持包括控制灌注、维持选择性渗透、预防血栓形成和参与免疫监视在内的稳态功能。血管细胞损伤会导致功能障碍，从而干扰这些过程。移植物血管细胞可被先天和适应性免疫的介质激活，参与移植物炎症，导致缺血/再灌注损伤和同种异体移植物排斥反应。不同形式的排斥反应可能以不同的方式影响移植物血管，从超急性排斥反应中的血栓形成和中性粒细胞炎症，到急性细胞介导或抗体介导排斥反应中的血管内皮炎/内膜动脉炎和纤维蛋白样坏死，再到慢性排斥反应中的弥漫性管腔狭窄。虽然一些针对宿主免疫系统的现有治疗方法确实会影响移植物血管细胞，但直接针对移植物血管可能为预防同种异体损伤和丧失创造新的机会。
