Prolonged function of macrophage, von Willebrand factor-deficient porcine pulmonary xenografts
Prolonged function of macrophage, von Willebrand factor-deficient porcine pulmonary xenografts
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DOI：
10.1111/j.1600-6143.2006.01603.x
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发表时间：
2007-01-01
影响因子：
8.8
通讯作者：
Davis, R. D.
中科院分区：
文献类型：
--
作者：
Cantu, E.;Balsara, K. R.;Davis, R. D.
猪血管性血友病因子（vWF）激活人类和灵长类动物血小板。利用左侧单肺移植模型，耗尽抗α Gal抗体的狒狒接受来自vWF缺陷型（n = 2）、MCP表达型（n = 5）、MCP PIM耗尽型（n = 5）、MCP PIM耗尽型（n = 6）、MCP PIM耗尽型（n = 7）和MCP PIM耗尽型（n = 8）的肺。三分之二的PM耗尽的pvWF缺陷移植物比任何先前报道的肺异种移植物（包括表达人补体调节蛋白的PM耗尽的异种移植物）存活更长。因此，就肺移植物存活而言，控制涉及pvWF的不良反应似乎与使用hMCP表达的补体调节同等重要或甚至更重要。然而，基于PIM充足的pvWF缺陷的肺异种移植物的快速失败，pVWF缺陷的肺异种移植物似乎对巨噬细胞介导的损伤特别敏感。这些数据提供了初步证据，vWF在使用PIM耗尽的hMCP器官的肺异种移植中观察到的“延迟”（24小时）功能障碍中起作用。
Porcine von Willebrand factor (vWF) activates human and primate platelets. Having determined the importance of pulmonary intravascular macrophages (PIMs) in pulmonary xenotransplantation, we evaluated whether, in the absence of PIMs, vWF might play a role in pulmonary xenograft dysfunction.Utilizing a left single-lung transplant model, baboons depleted of anti-alpha Gal antibodies received lungs from either vWF-deficient (n = 2); MCP-expressing (n = 5); MCP PIM-depleted (n = 5); or vWF-deficient PIM-depleted swine (n = 3).Two out of three of the PIM-depleted, pvWF deficient grafts survived longer than any previously reported pulmonary xenografts, including PIM-depleted xenografts expressing human complement regulatory proteins. Depletion of PIM's from vWF-deficient lungs, like depletion of PIM's from hMCP lungs, resulted in abrogation of the coagulopathy associated with pulmonary xenotransplantation.Thus, in terms of pulmonary graft survival, control of adverse reactions involving pvWF appears to be equally or even more important than is complement regulation using hMCP expression. However, based on the rapid failure of PIM-sufficient, pvWF-deficient pulmonary xenografts, pVWF-deficient pulmonary xenografts appear to be particularly sensitive to macrophage-mediated damage. These data provide initial evidence that vWF plays a role in the 'delayed' (24 h) dysfunction observed in pulmonary xenotransplantation using PIM depleted hMCP organs.