Membrane attack complex contributes to destruction of vascular integrity in acute lung allograft rejection
Membrane attack complex contributes to destruction of vascular integrity in acute lung allograft rejection
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DOI：
10.4049/jimmunol.169.8.4620
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发表时间：
2002-10-15
影响因子：
4.4
通讯作者：
Baldwin, WM
中科院分区：
文献类型：
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作者：
Nakashima, S;Qian, ZP;Baldwin, WM
众所周知，肺特别容易受到补体介导的损伤。补体C5a和补体末端成分(C5b-C9)形成的膜攻击复合体(MAC)均可引起非移植肺的急性肺窘迫。我们使用C6缺乏的大鼠来研究MAC是否对同种异体肺移植物造成损伤。将PVG.R8肺移植给MHC-I类不合的PVG.1U受体。C6(+)供者与C6(+)受者的同种异体移植在移植后7天发生排斥反应，并伴有严重的血管渗出和弥漫性肺泡出血(n=5)。AB和补体(C3d)沉积伴有广泛的血管内皮细胞损伤和血管内von Willebrand因子释放。相比之下，C6缺陷(C6(-))供者与C6(-)受体的同种异体肺移植存活13-17天(n=5)。在无C6的情况下，移植后7d可见ED1(+)巨噬细胞和CD8(+)T淋巴细胞在血管周围的单核细胞浸润，但血管内皮细胞处于静止状态，仅有少量von Willebrand因子释放，未见肺泡出血或水肿。分别从C6(-)供者到C6(+)受体(n=5)和从C6(+)供者到C6(-)受体(n=5)进行同种异体肺移植，以分离全身和局部C6产生的影响。C6(+)供者的肺移植到C6(-)受体的肺组织中，肺泡巨噬细胞增多，毛细血管损伤。同种异体肺移植的C6产生在mRNA和蛋白水平上得到证实。这些结果表明，MAC可引起移植肺血管损伤，损伤部位依赖于C6的来源。
The lung is known to be particularly susceptible to complement-mediated injury. Both C5a and the membrane attack complex (MAC), which is formed by the terminal components of complement (C5b-C9), can cause acute pulmonary distress in nontransplanted lungs. We used C6-deficient rats to investigate whether MAC causes injury to lung allografts. PVG.R8 lungs were transplanted orthotopically to MHC class I-incompatible PVG.1U recipients. Allografts from C6-sufficient (C6(+)) donors to C6(+) recipients were rejected with an intense vascular infiltration and diffuse alveolar hemorrhage 7 days after transplantation (n = 5). Ab and complement (C3d) deposition was accompanied by extensive vascular endothelial injury and intravascular release of von Willebrand factor. In contrast, lung allografts from C6-deficient (C6(-)) donors to C6(-) recipients survived 13-17 days (n = 5). In the absence of C6, perivascular mononuclear infiltrates of ED1(+) macrophages and CD8(+) T lymphocytes were present 7 days after transplantation, but vascular endothelial cells were quiescent, with minimal von Willebrand factor release and no evidence of alveolar hemorrhage or edema. Lung allografts were performed from C6(-) donors to C6(+) recipients (n = 5) and from C6(+) donors to C6(-) recipients (n = 5) to separate the effects of systemic and local C6 production. Lungs transplanted from C6(+) donors to C6(-) recipients had increased alveolar macrophages and capillary injury. C6 production by lung allografts was demonstrated at the mRNA and protein levels. These results demonstrate that MAC causes vascular injury in lung allografts and that the location of injury is dependent on the source of C6.