Does Galalpha(1,3)Gal still play a role in xenograft destruction after the production of Gal knockout pigs?

外科手术和免疫抑制技术的进步使器官移植成为治疗许多疾病的首选方法。然而，由于许多因素，合适的捐赠者的数量正在减少，但这主要是由于车祸死亡人数的减少。异种移植，即从人类以外的物种移植器官，现在被视为解决全球范围内缺乏合适人类捐赠者这一问题的可行解决方案。猪是最适合的，原因有很多。然而，问题是，所有人类都含有针对猪的天然抗体，这种抗体将在几分钟内导致排斥反应，因为抗体与移植细胞结合，并逆转其快速破坏(所谓的超急性排斥反应)。我们实验室最近的研究表明，大多数抗体(如果不是全部的话)都与移植的猪组织表面许多分子上的糖半乳糖发生反应。我们的研究表明，猪血管中存在大量这种物质，这保证了移植器官如肾脏、心脏和肝脏的早期排斥反应。培育出不表达半乳糖的基因敲除猪是异种移植成功的重要前提。最近，缺乏一种制造这种糖的酶的转基因猪已经被生产出来，但并不是所有的糖都被破坏了。我们最近描述了第二种新的酶，它也能制造这种糖。我们将研究这种酶在异种移植中的作用。这些研究将是生产可用于人类移植的猪的前奏。

Advances in surgical and immunosuppressive techniques has led to organ transplantation as the method of choice for the treatment of many diseases. However, the number of suitable donors is dwindling, due to many factors, but largely as a result of the reduction in deaths from car accidents. Xenotransplantation, the transplanting of organs from species other than humans, is now seen as a viable solution to the world wide problem of lack of supply of suitable human donors. The pig is the most suitable for a variety of reasons. However, the problem is that all humans contain natural antibodies to the pig which would lead to rejection within a few minutes as the antibodies bind to the transplant and reverse its rapid destruction (so called hyperacute rejection). Recent studies from our laboratory have indicated that most, if not all, of the antibodies react with the sugar - galactose present on many molecules on the surface of transplanted pig tissues. Our studies have indicated very large amounts of this material present in pig blood vessels - guaranteeing the early rejection of transplanted organs such as kidney, heart and liver. The production of knockout pigs which do not express the galactose sugar is an important pre-requisite for successful xenotransplantation. Recently knockout pigs which lack an enzyme that makes this sugar have been produced, but not all the sugar was destroyed. We have recently described a second novel enzyme that also makes this sugar. We will examine a role of this enzyme in xenotransplantation. These studies will be the prelude to the production of pigs which could be used for human transplantation.