Division of Organ Transplantation, Department of Surgery, Osaka University Graduate School of Medicine, Osaka, Japan.
Xenotransplantation. 2010 Jan-Feb;17(1):11-25. doi: 10.1111/j.1399-3089.2010.00569.x.
A number of institutes have reported on the successful production of alpha-galactosyltransferase knockout (GalT-KO) pigs. After producing such pigs, hyperacute rejection appeared to no longer be a problem. However, acute vascular rejection (AVR)/acute humoral xenograft rejection (AHXR) is defined as a rejection that begins within 24 h after transplantation and gradually destroys the graft. The origin of AVR/AHXR continues to be a controversial topic, but is generally thought to be initiated by xeno-reactive antibodies, including non-Gal antibodies and subsequent activation of the graft endothelium, the complement and the coagulation systems. The complement is activated via the classical pathway by non-Gal antigens and ischemia-reperfusion injury, via the alternative pathway, especially on islets, and via the lectin pathway. Therefore the complement system is still an important recognition and effector mechanism of AVR/AHXR. In addition, quite recently, based on the relationship between complement and coagulation systems, a new pathway has been proposed. All complement regulatory proteins (CRPs) have the ability to regulate complement activation in different ways. Therefore, to effectively protect xenografts against AVR/AHXR, it appears reasonable to employ not only one but several CRPs including anti-complement drugs. Non-Gal antigens, such as the Hanganutziu-Deicher antigen, is still present on GalT-KO grafts. The further assessment of antigens continues to be an important issue in the area of clinical xenotransplantation. The above conclusions suggest that the expression of human CRPs on GalT-KO grafts is necessary. Moreover, multilateral inhibition of complement activation is required in conjunction with the regulation of the coagulation system.
许多机构已经报告了成功生产α-半乳糖基转移酶敲除（GalT-KO）猪的情况。在生产出此类猪后，似乎不再存在超急性排斥反应的问题。然而，急性血管排斥反应（AVR）/急性体液异种移植排斥反应（AHXR）被定义为在移植后 24 小时内开始并逐渐破坏移植物的排斥反应。AVR/AHXR 的起源仍然是一个有争议的话题，但通常认为是由异种反应性抗体引起的，包括非 Gal 抗体和随后对移植物内皮细胞、补体和凝血系统的激活。补体通过非 Gal 抗原和缺血再灌注损伤通过经典途径激活，通过替代途径（特别是在胰岛中）和凝集素途径激活。因此，补体系统仍然是 AVR/AHXR 的重要识别和效应机制。此外，就在最近，基于补体和凝血系统之间的关系，提出了一种新途径。所有补体调节蛋白（CRPs）都具有以不同方式调节补体激活的能力。因此，为了有效保护异种移植物免受 AVR/AHXR 的侵害，似乎不仅可以使用一种，而且可以使用包括抗补体药物在内的几种 CRP。GalT-KO 移植物上仍然存在非 Gal 抗原，如 Hanganutziu-Deicher 抗原。进一步评估抗原仍然是临床异种移植领域的一个重要问题。上述结论表明，在 GalT-KO 移植物上表达人 CRP 是必要的。此外，需要与凝血系统调节相结合，进行补体激活的多方面抑制。
