Both apoptosis and complement membrane attack complex deposition are major features of murine acute graft-vs.-host disease
Both apoptosis and complement membrane attack complex deposition are major features of murine acute graft-vs.-host disease
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DOI：
10.1016/j.yexmp.2005.03.007
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发表时间：
2005-10-01
影响因子：
3.6
通讯作者：
Via, CS
中科院分区：
文献类型：
--
作者：
Niculescu, F;Niculescu, T;Via, CS
急性移植物抗宿主病 (GVHD) 的亲代 F1 小鼠模型 (P -> F1) 是人类急性 GVHD 的有用模型，因为它允许研究 T 细胞对病理学的贡献，而无需预处理方案的复杂影响。为了确定该模型与人类 GVHD 的相似性，我们评估了通常参与人类急性 GVHD 的器官（皮肤、肝脏）和不太常见的器官（脾、肾、肺）的损伤。在早期（2周）、中期（3个月）和晚期（6个月）时间点对小鼠进行组织学评估。基于 Fas 配体杀伤和补体沉积在同种异体移植排斥中的新作用，我们将组织特异性 TUNEL 阳性细胞凋亡和补体 (C5b-9) 沉积的量与组织病理学变化相关联。我们的结果表明，该模型中发生的急性 GVHD 与骨髓移植后人类中发生的急性 GVHD 在组织学上具有惊人的相似性。此外，发现 C5b-9 沉积和凋亡细胞积累与急性 GVHD 小鼠主要器官的组织损伤平行，尽管并非所有器官都表现出相同的动力学模式。这些结果表明了适应性免疫和先天免疫在这种 GVHD 模型中的作用，并支持其在非清髓性环境中模拟人类急性 GVHD 的用途。 (c) 2005 Elsevier Inc. 保留所有权利。
The parent-into-F1 mouse model (P -> F1) of acute graft-vs.-host disease (GVHD) is a useful model of human acute GVHD because it allows the study of the T cell contribution to pathology without the complicating effects of conditioning regimens. To determine the similarity of this model to human GVHD, we assessed injury in organs typically involved in human acute GVHD (skin, liver) and less typically involved organs (spleen, kidney, lung). Mice were assessed histologically at early (2 weeks), intermediate (3 months) and late (6 month) time points. Based on the emerging roles of Fas ligand killing and complement deposition in allograft rejection, we correlated the amount of tissue specific TUNEL positive apoptosis and deposition of complement (C5b-9) with histopathologic changes. Our results indicate a striking similarity histologically between acute GVHD occurring in this model and in humans following bone marrow transplant. Moreover, C5b-9 deposition and apoptotic cell accumulation were found to parallel tissue injury in major organs of acute GVHD mice, although not all organs exhibited the same kinetic pattern. These results indicate a role for both adaptive immunity and innate immunity in this model of GVHD and support its use in modeling human acute GVHD in the nonmyeloablative setting. (c) 2005 Elsevier Inc. All rights reserved.