Complement regulation in the GalT KO era

被引:59
作者
Miyagawa, Shuji [1 ]
Yamamoto, Aki [1 ]
Matsunami, Katsuyoshi [1 ]
Wang, Dandan [1 ]
Takama, Yuichi [1 ]
Ueno, Takehisa [1 ]
Okabe, Masaru [2 ]
Nagashima, Hiroshi [3 ]
Fukuzawa, Masahiro [1 ]
机构
[1] Osaka Univ, Grad Sch Med, Dept Surg, Div Organ Transplantat, Osaka, Japan
[2] Osaka Univ, Microbial Dis Res Inst, Osaka, Japan
[3] Meiji Univ, Dept Life Sci, Kanagawa, Japan
关键词
complement activation; complement regulatory protein; GalT-KO pig; non-Gal antigen; pig islets; DECAY-ACCELERATING FACTOR; MEMBRANE COFACTOR PROTEIN; MEDIATED INFLAMMATORY REACTION; N-GLYCOLYLNEURAMINIC ACID; GENE-KNOCKOUT PIGS; HUMAN NATURAL ANTIBODIES; DISCORDANT XENOGRAFT REJECTION; CLINICAL ISLET TRANSPLANTATION; HANGANUTZIU-DEICHER ANTIGENS; HUMAN-ERYTHROCYTE MEMBRANE;
D O I
10.1111/j.1399-3089.2010.00569.x
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
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.
引用
收藏
页码:11 / 25
页数:15
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