猪到人异种心脏移植超急性排斥反应的研究
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摘要
【目的】
随着基础研究的不断深入及外科技术的日益完善，器官移植已成为救治多种器官功能衰竭患者生命的首选方法；然而随着人体器官移植适应症的增加和移植成功率的提高，器官移植手术数量大幅增加，造成临床上器官来源呈现严重短缺。为了解决这个问题，近年来，异种器官作为缓解人体器官短缺的有效措施之一受到了人们的关注。在异种动物之中，由于猪器官的生理解剖特点及脏器大小与人类十分接近，被认为是异种器官移植的理想供体，但猪→人异种器官移植需要克服的首要免疫学障碍是超急性排斥反应。其发生的主要机理是人体内预先存在的天然抗体识别猪细胞表面的异种抗原表位—半乳糖α1，3半乳糖(galactoseα1，3 galsctose，Galα1，3 Gal)，从而激活补体而引起血小板聚集，形成血栓，导致移植器官的失功。
水苏糖是从一种叫做地灵(Stachys floridona)的根茎中提取的α半乳糖苷类非还原性低聚糖，简单的结构表示为：果糖—葡萄糖—半乳糖—半乳糖(Galα1，6-Galα1，6-Gluβ1，2-Fructose)，分子式为C_(24)H_(42)O_(21)，分子量为666.59，无毒，易溶于水。水苏糖具有α-Gal抗原相似的分子结构，理论上具有抑制超急性排斥反应的作用。本实验旨在从细胞及器官水平，观察水苏糖对猪到人异种心脏移植超急性排斥反应的抑制作用。
【方法】
首先，将传代培养的猪髋动脉内皮细胞PIEC暴露于人血浆中，同时与水苏糖或PBS(空白对照)共同孵育后，采用MTT法检测细胞的存活率，从而观察水苏糖对PIEC的保护作用。为观察对整体器官的效应，我们建立了离体猪心脏体外灌流的超急性排斥反应模型，检测人血液单独灌注组及人血液加水苏糖灌注组心脏组织的病理及其免疫组化(IgG及IgM在组织的沉积)的变化，以观察水苏糖对猪到人异种心脏移植超急性排斥反应的抑制作用。
【结果】
1．MTT法检测水苏糖处理组的PIEC的相对存活率随着水苏糖浓度的增加而升高。说明水苏糖对PIEC有保护作用。
2．成功地建立了人血液体外灌注猪离体心脏的超急性排斥反应的模型。
3．灌注猪心脏的存活时间：水苏糖加人血液灌注组的存活时间明显长于人血液单独灌注组。人血液单独灌注猪心脏的平均存活时间为(9.5±2.5)min，而人血液加水苏糖灌注猪心脏的平均存活时间为(46.8±8.1)min。
4．灌注猪心脏组织的病理学检查：水苏糖加人血液灌注组的猪心脏未发生超急性排斥反应；而人血液单独灌注组猪的心脏的心肌间质弥漫性出血、水肿，血管扩张，内皮细胞肿胀、坏死，细胞间质散在单核细胞浸润，证明发生了超急性排斥反应。
5．灌注猪心脏组织的免疫组化检测：水苏糖加人血液灌注组的猪心脏心肌血管内皮未见IgG及IgM的沉积；而人血液单独灌注组见明显沉积。
【结论】
上述实验结果说明水苏糖可以与人血液中的天然抗体竞争性结合，具有抑制异种移植超急性排斥反应发生的作用，从而对暴露于人血液中的PIEC及猪心脏有保护作用。
【目的】
器官移植已经成为许多终术期器官疾患的主要治疗措施之一，但它的广泛应用引起了人体可移植器官的严重短缺，所以人们开始认真地考虑异种移植。目前，猪到人异种移植已经被公认为解决器官短缺的有效措施。但猪到人的异种移植存在很多免疫学障碍。除了猪到人的超急性排斥反应、急性血管性排斥、和慢性排斥反应外，猪和人的血型不相容等因素也可能是引起异种器官移植物失功的原因之一。所以本实验旨在检测猪红细胞上是否表达与人类相似的ABO血型抗原。
【方法】
1．猪红细胞表面A、B抗原的检测
采用细胞凝集法。猪红细胞和抗-A、抗-B抗体在血凝板中反应，红细胞凝集时，成网环状沉积在血凝板底部，说明具有相应抗原；不凝集时形成点状沉淀，说明不表达相应抗原。
2．猪血浆中抗-A、抗-B抗体的检测
采用血型反定型法检测猪血浆中的血型抗体。将猪的血浆预先与人类O型红细胞孵育，以去除猪血浆中存在抗人抗体引起的非特异型凝集。
【结果】
1．猪红细胞表面A、B抗原的检测
我们检测了72头不同种猪的红细胞，未检测到A或B抗原。
2．猪血浆中抗-A、抗-B抗体的检测
我们检测了72头猪血浆中的抗-A、抗-B抗体，其中37头猪检测到抗-A和抗-B抗体，14头猪检测到抗-A抗体，3头猪检测到抗-B抗体，18头猪未检测到抗-A或抗-B抗体。
【结论】
上述实验结果说明在我们检测的72头猪中，红细胞上不表达与人类相似的血型抗原，但猪的血浆中存在血型抗体。我们检测的72头猪的血浆中，51.4％具有抗-A和抗-B抗体，19.4％具有抗-A抗体，4.2％具有抗-B抗体，25％不具有抗-A或抗-B抗体。
Objective: Although allotransplantation, with its great basic and clinical success, has become the potential treatment to end-stage organ failure, it also has resulted in a shortage of available organs from deceased human donors. In recent years, attention has been drawn towards xenotransplantation. Pig is investigated as the most likely species to provide organs for human because the anatomy and organ size of pig is similar with human. However, major problems remain to be resolved before successful clinical xenotransplantation can be initiated. The initial immunological barrier of pig-to-human xenotransplantation is hyperacute rejection, which is initiated by natural preformed antibodies directed a carbohydrate epitopes (α-Gal) on the pig vascular endothelium. The binding of antibody to antigen activates the complement cascade, which leads to graft damage.
Stachyose is extracted from the root of stachys floridana. It is a kind of nonreductive oligosaccharides. Its constitutional formula is fructose-glucose-galactose-galactose with molecular formula C_(24)H_(42)O_(21), and molecular weight is 666.59. Stachyose is not toxic and water-soluble. It can inhibit hyperacute rejection of xenotransplantation theoretically since it contains the structure of α-Gal which is similar with the xenogenic antigenic epitope of galactose-α1,3-galacotse. Our
objective was to investigate the inhibition of stachyose on hyperacute rejection from cell and organ experiments.
Methods: PIEC was exposed in human blood plasma and incubated with stachyose or PBS. Then we employed the method of MTT to determine the survival rate of cells, to investigate the protection of stachyose on PIEC. Construct a model of hyperacute rejection of in vitro perfusion pig heart. To investigate the inhibition of stachyose on hyperacute rejection. We determine the histopathobiology and immunohistology of pig hearts which perfused with or without stachyose.
Results:
1. The survival rate of PIEC increased as the concentration of stachyose increased.
2. We have established the model of hyperacute rejection of in vitro perfusion pig heart successfully.
3. The survival time of human blood plus stachyose group were longer than control group. The mean time of perfusion hearts in human blood group was (9.5±2.5) min while in human blood plus stachyose perfusion group was (46.8±8.1) min.
4. Histopathological studies showed that haemorrhagia, edema, necrosis of endothelial cell, distension of blood vessel were found in human blood perfusion group while there were no obvious pathological changes in human blood plus stachyose group.
5. Immunohistochemistry studies also indicated there were obvious deposit of IgG and IgM in human blood perfusion group while in human blood plus stachyose perfusion group no deposit of IgG or IgM were found.
Conclusion: Stachyose can competitively bind to natural anti-Gal antibody in human blood, inhibit hyperacute rejection. Stachyose can protect PIEC and pig heart from hyperacute rejection.
Objective
Allotransplantation, as the most effective measure to end-stage organ failure, has resulted in shortage of organs. Attention has been drawn towards xenotransplantation. Xenotransplantation from pig to human is a potential solution to the worldwide shortage of organs. However, it has many immunology barriers. The imcompatibility of blood type between human and pig may be the reason to failure of organ xenotransplantation, in addition to hyperacute rejection, acute vascular rejection and chronic rejection. The objective of this article was to determine the ABO blood antigen on pig erythrocyte.
Methods
1. Determine A or B antigen on pig erythrocyte
Employ the method of cell agglutination. Pig erythrocyte and anti-A or anti-B was added to the agglutination plates. The agglutination of pig erythrocyte was visible when erythrocyte distributed on the bottom of the wells to form blood dumps. While erythrocyte precipitated as a small dot as no agglutination happened, which proved that no corresponding antigen was on erythrocyte.
2. Determine anti-A or anti-B in plasma of pig
Employ the method of reverse typing to determine the blood antibody in plasma of pig. The plasma of pig was pre-absorbed with packed human type O erythrocyte to remove non-specific binding from anti-human heteroagglutinins.
Results
1. Detection of the A or B antigen on the surface of porcine erythrocytes
We did not found the blood antigen on pig erythrocyte (n=72).
2. Determine anti-A or anti-B in plasma of pig
We determined anti-A or anti-B antibodies in plasma of 72 pigs. 37 pigs were found both anti-A and anti-B antibodies, 14 pigs were found anti-A antibodies, only 3 pigs were found anti-B antibodies, and 18 pigs were found neither anti-A nor anti-B antibodies.
Conlusion
From our experiments, we have demonstrated:
Although pig erythrocytes do not express ABO blood antigen which is similar with human, blood group antibodies are in the plasma of pig. We have determined plasma of 72 pigs, 51.4% was found anti-A and anti-B antibody in their plasma; 19.4 was found anti-A antibody; 4.2% was found anti-B antibody; 25% was found neither anti-A nor anti-B antibody.
随着基础研究的不断深入及外科技术的日益完善，器官移植已成为救治多种器官功能衰竭患者生命的首选方法；然而随着人体器官移植适应症的增加和移植成功率的提高，器官移植手术数量大幅增加，造成临床上器官来源呈现严重短缺。为了解决这个问题，近年来，异种器官作为缓解人体器官短缺的有效措施之一受到了人们的关注。在异种动物之中，由于猪器官的生理解剖特点及脏器大小与人类十分接近，被认为是异种器官移植的理想供体，但猪→人异种器官移植需要克服的首要免疫学障碍是超急性排斥反应。其发生的主要机理是人体内预先存在的天然抗体识别猪细胞表面的异种抗原表位—半乳糖α1，3半乳糖(galactoseα1，3 galsctose，Galα1，3 Gal)，从而激活补体而引起血小板聚集，形成血栓，导致移植器官的失功。
水苏糖是从一种叫做地灵(Stachys floridona)的根茎中提取的α半乳糖苷类非还原性低聚糖，简单的结构表示为：果糖—葡萄糖—半乳糖—半乳糖(Galα1，6-Galα1，6-Gluβ1，2-Fructose)，分子式为C_(24)H_(42)O_(21)，分子量为666.59，无毒，易溶于水。水苏糖具有α-Gal抗原相似的分子结构，理论上具有抑制超急性排斥反应的作用。本实验旨在从细胞及器官水平，观察水苏糖对猪到人异种心脏移植超急性排斥反应的抑制作用。
【方法】
首先，将传代培养的猪髋动脉内皮细胞PIEC暴露于人血浆中，同时与水苏糖或PBS(空白对照)共同孵育后，采用MTT法检测细胞的存活率，从而观察水苏糖对PIEC的保护作用。为观察对整体器官的效应，我们建立了离体猪心脏体外灌流的超急性排斥反应模型，检测人血液单独灌注组及人血液加水苏糖灌注组心脏组织的病理及其免疫组化(IgG及IgM在组织的沉积)的变化，以观察水苏糖对猪到人异种心脏移植超急性排斥反应的抑制作用。
【结果】
1．MTT法检测水苏糖处理组的PIEC的相对存活率随着水苏糖浓度的增加而升高。说明水苏糖对PIEC有保护作用。
2．成功地建立了人血液体外灌注猪离体心脏的超急性排斥反应的模型。
3．灌注猪心脏的存活时间：水苏糖加人血液灌注组的存活时间明显长于人血液单独灌注组。人血液单独灌注猪心脏的平均存活时间为(9.5±2.5)min，而人血液加水苏糖灌注猪心脏的平均存活时间为(46.8±8.1)min。
4．灌注猪心脏组织的病理学检查：水苏糖加人血液灌注组的猪心脏未发生超急性排斥反应；而人血液单独灌注组猪的心脏的心肌间质弥漫性出血、水肿，血管扩张，内皮细胞肿胀、坏死，细胞间质散在单核细胞浸润，证明发生了超急性排斥反应。
5．灌注猪心脏组织的免疫组化检测：水苏糖加人血液灌注组的猪心脏心肌血管内皮未见IgG及IgM的沉积；而人血液单独灌注组见明显沉积。
【结论】
上述实验结果说明水苏糖可以与人血液中的天然抗体竞争性结合，具有抑制异种移植超急性排斥反应发生的作用，从而对暴露于人血液中的PIEC及猪心脏有保护作用。
【目的】
器官移植已经成为许多终术期器官疾患的主要治疗措施之一，但它的广泛应用引起了人体可移植器官的严重短缺，所以人们开始认真地考虑异种移植。目前，猪到人异种移植已经被公认为解决器官短缺的有效措施。但猪到人的异种移植存在很多免疫学障碍。除了猪到人的超急性排斥反应、急性血管性排斥、和慢性排斥反应外，猪和人的血型不相容等因素也可能是引起异种器官移植物失功的原因之一。所以本实验旨在检测猪红细胞上是否表达与人类相似的ABO血型抗原。
【方法】
1．猪红细胞表面A、B抗原的检测
采用细胞凝集法。猪红细胞和抗-A、抗-B抗体在血凝板中反应，红细胞凝集时，成网环状沉积在血凝板底部，说明具有相应抗原；不凝集时形成点状沉淀，说明不表达相应抗原。
2．猪血浆中抗-A、抗-B抗体的检测
采用血型反定型法检测猪血浆中的血型抗体。将猪的血浆预先与人类O型红细胞孵育，以去除猪血浆中存在抗人抗体引起的非特异型凝集。
【结果】
1．猪红细胞表面A、B抗原的检测
我们检测了72头不同种猪的红细胞，未检测到A或B抗原。
2．猪血浆中抗-A、抗-B抗体的检测
我们检测了72头猪血浆中的抗-A、抗-B抗体，其中37头猪检测到抗-A和抗-B抗体，14头猪检测到抗-A抗体，3头猪检测到抗-B抗体，18头猪未检测到抗-A或抗-B抗体。
【结论】
上述实验结果说明在我们检测的72头猪中，红细胞上不表达与人类相似的血型抗原，但猪的血浆中存在血型抗体。我们检测的72头猪的血浆中，51.4％具有抗-A和抗-B抗体，19.4％具有抗-A抗体，4.2％具有抗-B抗体，25％不具有抗-A或抗-B抗体。
Objective: Although allotransplantation, with its great basic and clinical success, has become the potential treatment to end-stage organ failure, it also has resulted in a shortage of available organs from deceased human donors. In recent years, attention has been drawn towards xenotransplantation. Pig is investigated as the most likely species to provide organs for human because the anatomy and organ size of pig is similar with human. However, major problems remain to be resolved before successful clinical xenotransplantation can be initiated. The initial immunological barrier of pig-to-human xenotransplantation is hyperacute rejection, which is initiated by natural preformed antibodies directed a carbohydrate epitopes (α-Gal) on the pig vascular endothelium. The binding of antibody to antigen activates the complement cascade, which leads to graft damage.
Stachyose is extracted from the root of stachys floridana. It is a kind of nonreductive oligosaccharides. Its constitutional formula is fructose-glucose-galactose-galactose with molecular formula C_(24)H_(42)O_(21), and molecular weight is 666.59. Stachyose is not toxic and water-soluble. It can inhibit hyperacute rejection of xenotransplantation theoretically since it contains the structure of α-Gal which is similar with the xenogenic antigenic epitope of galactose-α1,3-galacotse. Our
objective was to investigate the inhibition of stachyose on hyperacute rejection from cell and organ experiments.
Methods: PIEC was exposed in human blood plasma and incubated with stachyose or PBS. Then we employed the method of MTT to determine the survival rate of cells, to investigate the protection of stachyose on PIEC. Construct a model of hyperacute rejection of in vitro perfusion pig heart. To investigate the inhibition of stachyose on hyperacute rejection. We determine the histopathobiology and immunohistology of pig hearts which perfused with or without stachyose.
Results:
1. The survival rate of PIEC increased as the concentration of stachyose increased.
2. We have established the model of hyperacute rejection of in vitro perfusion pig heart successfully.
3. The survival time of human blood plus stachyose group were longer than control group. The mean time of perfusion hearts in human blood group was (9.5±2.5) min while in human blood plus stachyose perfusion group was (46.8±8.1) min.
4. Histopathological studies showed that haemorrhagia, edema, necrosis of endothelial cell, distension of blood vessel were found in human blood perfusion group while there were no obvious pathological changes in human blood plus stachyose group.
5. Immunohistochemistry studies also indicated there were obvious deposit of IgG and IgM in human blood perfusion group while in human blood plus stachyose perfusion group no deposit of IgG or IgM were found.
Conclusion: Stachyose can competitively bind to natural anti-Gal antibody in human blood, inhibit hyperacute rejection. Stachyose can protect PIEC and pig heart from hyperacute rejection.
Objective
Allotransplantation, as the most effective measure to end-stage organ failure, has resulted in shortage of organs. Attention has been drawn towards xenotransplantation. Xenotransplantation from pig to human is a potential solution to the worldwide shortage of organs. However, it has many immunology barriers. The imcompatibility of blood type between human and pig may be the reason to failure of organ xenotransplantation, in addition to hyperacute rejection, acute vascular rejection and chronic rejection. The objective of this article was to determine the ABO blood antigen on pig erythrocyte.
Methods
1. Determine A or B antigen on pig erythrocyte
Employ the method of cell agglutination. Pig erythrocyte and anti-A or anti-B was added to the agglutination plates. The agglutination of pig erythrocyte was visible when erythrocyte distributed on the bottom of the wells to form blood dumps. While erythrocyte precipitated as a small dot as no agglutination happened, which proved that no corresponding antigen was on erythrocyte.
2. Determine anti-A or anti-B in plasma of pig
Employ the method of reverse typing to determine the blood antibody in plasma of pig. The plasma of pig was pre-absorbed with packed human type O erythrocyte to remove non-specific binding from anti-human heteroagglutinins.
Results
1. Detection of the A or B antigen on the surface of porcine erythrocytes
We did not found the blood antigen on pig erythrocyte (n=72).
2. Determine anti-A or anti-B in plasma of pig
We determined anti-A or anti-B antibodies in plasma of 72 pigs. 37 pigs were found both anti-A and anti-B antibodies, 14 pigs were found anti-A antibodies, only 3 pigs were found anti-B antibodies, and 18 pigs were found neither anti-A nor anti-B antibodies.
Conlusion
From our experiments, we have demonstrated:
Although pig erythrocytes do not express ABO blood antigen which is similar with human, blood group antibodies are in the plasma of pig. We have determined plasma of 72 pigs, 51.4% was found anti-A and anti-B antibody in their plasma; 19.4 was found anti-A antibody; 4.2% was found anti-B antibody; 25% was found neither anti-A nor anti-B antibody.
引文
[1] David K.C. Cooper. xenotransplantation: the road ahead. Current opinion in organ transplantation. 2006, 11: 151-153
[2] Saadi S, Platt JL. Immunology of xenotransplantation. Life Sci. 1998, 62 (5): 365-387.
[3] Ezzelarab M, Ayares D, Cooper DK. Carbohydrates in xenotransplantation. Immunol Cell Biol. 2005, 83(4): 396-404.
[4] Galili U, Shohet SB, Kobrin E, Stults CL, Macher BA. Man, apes, and Old World monkeys differ from other mammals in the expression of alpha-galactosyl epitopes on nucleated cells. J Biol Chem. 1988, 263(33): 17755-17762.
[5] Kobayashi T, Cooper DK. Anti-Gal, alpha-Gal epitopes, and xenotransplantation. Subcell Biochem. 1999, 32: 229-257.
[6] Dalmasso AP, Vercellotti GM, Fischel RJ, et al. Mechanism of complement activation in the hyperacute rejection of porcine organs transplanted into primate recipients. Am J Pathol. 1992, 140(5): 1157-1166.
[7] Cooper DK, Good AH, Koren E, Oriol R, Malcolm AJ, Ippolito RM, Neethling FA, Ye Y, Romano E. Identification of alpha-galactosyl and other carbohydrate epitopes that are bound by human anti-pig antibodies: relevance to discordant xenografting in man. Transpl Immunol. 1993, 1(3): 198-205
[8] Good AH, Cooper DK, Malcolm AJ, Ippolito RM, Koren E, Neethling FA, Ye Y, Zuhdi N, Lamontagne LR. Identification of carbohydrate structures that bind human antiporcine antibodies: implications for discordant xenografting in humans. Transplant Proc. 1992, 24(2): 559-562
[9] Milland J, Christiansen D, Sandrin MS. Alphal,3-galactosyltransferase knockout pigs are available for xenotransplantation: are glycosyltransferases still relevant?. Immunol Cell Biol. 2005, 83(6): 687-693.
[10] Lang J, Zhan J, Xu L, et al. Identification of peptide mimetics of xenoreactive α-Gal antigenic epitope by phage display. Biochem Biophys Res Commun. 2006, 344(1): 214-220.
[11] Neethling FA, Koren E, Ye Y, et al. Protection of pig kidney(PK15) cells by from the cytotoxic effect of anti-pig antibodies by α-galactosyl oligosaccharides. Transplantation. 1994, 57(6): 959-963
[12] Sandrin MS, Vaughan HA, Dabkowski PL, et al. Anti-pig IgM antibodies in human serum react predominantly with Gal(alpha 1-3)Gal epitopes. Proc Natl Acad Sci U S A. 1993,90(23): 11391-11395
[13] Evidence that intravenously administered alpha-galactosyl carbohydrates reduce baboon serum cytotoxicity to pig kidney cells (PK15) and transplanted pig hearts. Ye Y, Neethling FA, Niekrasz M, Koren E, Richards SV, Martin M, Kosanke S, Oriol R, Cooper DK. Transplantation. 1994, 58(3): 330-337.
[14] Manji RA, Manji JS, Koshal A, Korbutt GS, Rajotte RV. Human ABO blood group is important in survival and function of porcine working hearts. Am J Transplant. 2003, 3(3): 286-293
[15] Factors in xenograft rejection. Robson SC, Schulte am Esch J 2nd, Bach FH. Ann N Y Acad Sci. 1999, 875: 261-276.
[16] Lawson JH, Platt JL. Molecular barriers to xenotransplantation. Transplantation. 1996, 62(3): 303-310
[17] Koren E, Neethling FA, Richards S, Koscec M, Ye Y, Zuhdi N, Cooper DK. Binding and specificity of major immunoglobulin classes of preformed human anti-pig heart antibodies. Transpl Int. 1993, 6(6): 351-353.
[18] Roos A, Essers M, van Gijlswijk-Janssen D, Bovin NV, Daha MR. Both IgGand IgM anti-pig antibodies induce complement activation and cytotoxicity. Xenotransplantation. 2001, 8(1): 3-14
[19] Schaapherder AF, Daha MR, te Bulte MT, van der Woude FJ, Gooszen HG. Antibody-dependent cell-mediated cytotoxicity against porcine endothelium induced by a majority of human sera. Transplantation. 1994, 57(9): 1376-1382.
[20] Platt JL, Fischel RJ, Matas AJ, et al. Immunopathology of hyperacute xenograft rejection in a swine-to-primate model. Transplantation. 1991, 52(2): 214-220.
[1] Chen RH, Mitchell RN, Kadner A, Adams DH. Differential galactose alpha(1,3) galactose expression by porcine cardiac vascular endothelium. Xenotransplantation. 1999,6(3): 169-172.
[2] Zhu A, Hurst R. Anti-N-glycolylneuraminic acid antibodies identified in healthy human serum. Xenotransplantation. 2002, 9(6): 376-381.
[3] Manji RA, Manji JS, Koshal A, Korbutt GS, Rajotte RV. Human ABO blood group is important in survival and function of porcine working hearts. Am J Transplant. 2003, 3(3): 286-293.
[4] Leight GS, Kirkman R, Rasmusen BA, Rosenberg SA, Sachs DH, Terrill R, Williams GM. Transplantation in miniature swine. III: effects of MSLA and A-O blood group matching on skin allograft survival. Tissue Antigens. 1978 ,12(2):65-74.
[5] Rydberg L. ABO-incompatibility in solid organ transplantation. Transfus Med. 2001, 11(4): 325-342.
[6] Wu A, Buhler LH, Cooper DK. ABO-incompatible organ and bone marrow transplantation: current status. Transpl Int. 2003,16(5): 291-299.
[7] Rydberg L, Molne J, Strokan V, Svalander CT, Breimer ME. Histo-blood group A antigen expression in pig kidneys-implication for ABO incompatible pig-to-human xenotransplantation. Scand J Urol Nephrol. 2001, 35(1): 54-62.
[8] ANDRESEN E. Blood groups in pigs. Ann N Y Acad Sci. 1962, 97: 205-25.
[9] Gonzalez A, Friend M, Moreno A, Pintado CO, Vogeli P, Llanes D. A monoclonal antibody to swine erythrocytes recognizes the B blood group on the major glycophorin. Animal genetics. 1995, 26(5): 351-353.
[10] Phelps CJ, Koike C, Vaught TD, Boone J, Wells KD, Chen SH, Ball S, Specht SM, Polejaeva IA, Monahan JA, Jobst PM, Sharma SB, Lamborn AE, Garst AS, Moore M, Demetris AJ, Rudert WA, Bottino R, Bertera S, Trucco M, Starzl TE, Dai Y, Ayares DL. Production of alphal,3-galactosyltransferase -deficient pigs. Science. 2003, 299(5605): 411-414.
[11] Kuwaki K, Tseng YL, Dor FJ, Shimizu A, Houser SL, Sanderson TM, Lancos CJ, Prabharasuth DD, Cheng J, Moran K, Hisashi Y, Mueller N, Yamada K, Greenstein JL, Hawley RJ, Patience C, Awwad M, Fishman JA, Robson SC, Schuurman HJ, Sachs DH, Cooper DK. Heart transplantation in baboons using alphal,3-galactosyltransferase gene-knockout pigs as donors: initial experience. Nat Med. 2005, 11(1): 29-31.
[12] Yamada K, Yazawa K, Shimizu A, Iwanaga T, Hisashi Y, Nuhn M, O'Malley P, Nobori S, Vagefi PA, Patience C, Fishman J, Cooper DK, Hawley RJ, Greenstein J, Schuurman HJ, Awwad M, Sykes M, Sachs DH. Marked prolongation of porcine renal xenograft survival in baboons through the use of alphal,3-galactosyltransferase gene-knockout donors and the cotransplantation of vascularized thymic tissue. Nat Med. 2005, 11(1): 32-34.
[13] Hanagata G, Gasa S, Sako F, Makita A. Human blood group A and H glycolipids in porcine plasma. FEBS Lett. 1990, 261(2): 312-314.
[14] Makita A, Gasa S, Sako F, Hanagata G. Glycosphingolipids of porcine blood: human blood group A and H antigens with type 1 chain in erythrocytes and plasma. Indian J Biochem Biophys. 1990, 27(6): 402-410.
[15] Coombs RR, Goodwin RF. The blood groups of the pig. J Comp Pathol. 1956, 66(4): 317-331.
[1] Eto T, Ichikawa Y, Nishimura K, Ando S, Yamakawa T. Chemistry of lipid of the posthemyolytic residue or stroma of erythrocytes. ⅩⅤⅠ. Occurrence of ceramidepentasaccharide in the membrane of erythrocytes and reticulocytes of rabbit. J. Biochem. 1968, 64(2): 205-213.
[2] Kobayashi T, Cooper DK. Anti-Gal, alpha-Gal epitopes, and xenotransplantation. Subcell Biochem. 1999, 32: 229-257.
[3] Raymond H. Chen, Richard N. Mitchell, Alexander Kadner, David H. Adams. Differential galactose α(1, 3) galactose expression by porcine cardiac vascular endothelium. Xenotransplantation. 1999, 6(3): 169-172.
[4] 曾令宇，李幼平。猪到人异种移植超急性排斥反应的靶抗原。中国普外基与临床杂志．2003，10(4)：422-425．
[5] Manji RA, Manji JS. Koshal A, Korbutt GS, Rajotte RV. Human ABO bloodgroup is important in survival and function of porcine working hearts. Am J Transplant. 2003, 3(3): 286-293.
[6] Galili U, Shohet SB, Kobrin E, Stults CL, Macher BA. Man, apes, and Old World monkeys differ from other mammals in the expression of alpha-galactosyl epitopes on nucleated cells. J Biol Chem. 1988, 263(33): 17755-17762.
[7] Cooper DK, Good Aid, Koren E, Oriol R, Malcolm AJ, Ippolito RM, Neethling FA, Ye Y, Romano E. Zuhdi N. Identification of alpha-galactosyl and other carbohydrate epitopes that are bound by human anti-pig antibodies: relevance to discordant xenografting in man. Transpl Immunol. 1993, 1(3): 198-205.
[8] Good AH, Cooper DK, Malcolm AJ, Ippolito RM, Koren E, Neethling FA, Ye Y, Zuhdi N, Lamontagne LR. Identification of carbohydrate structures that bind human antiporcine antibodies: implications for discordant xenografting in humans. Transplant Proc. 1992. 24(2): 559-562.
[9] McMorrow IM, Comrack CA. Sachs DH, DerSimonian H. Heterogeneity of human anti-pig natural antibodies crossreactive with the Gal(alphal,3)Galactose epitope. Transplantation. 1997, 64(3): 501-10.
[10] Roos A, Essers M, van Gijiswijk-Janssen D, Bovin NV, Daha MR. Both IgG and IgM anti-pig antibodies induce complement activation and cytotoxicity. Xenotransplantation. 2001, 8(1): 3-14.
[11] Artrip JH, Kwiatkowski P, Michler RE, Wang SF, Tugulea S, Ankersmit J, Chisholm L, McKenzie IF, Sandrin MS, Itescu S. Target cell susceptibility to lysis by human natural killer cells is augmented by alpha(1,3)-galactosyltrans -ferase and reduced by alpha(l,2)-fucosyltransferase. J Biol Chem. 1999, 274(16): 10717-10722.
[12] Schaapherder AF, Daha MR, te Bulte MT, van der Woude FJ,Gooszen HG. Antibody-dependent cell-mediated cytotoxicity against porcine endothelium induced by a majority of human sera. Transplantation. 1994, 57(9): 1376-1382.
[13] Galili U, LaTemple DC, Walgenbach AW, Stone KR. Porcine and bovine cartilage transplants in cynomolgus monkey: II.Changes in anti-Gal response during chronic rejection. Transplantation. 1997, 63(5): 646-651
[14] Gollackner B. Ryan D, Knosalla C. Basker M, Alwayn IP, Harper D, Salomon G, Mauiyyedi S, Correa L, Thall A. Cooper DK . An exploratory investigation of the effect of arsenic trioxide on anti-Gal antibody production in baboons. Xenotransplantation. 2003. 10(1): 80 - 87.
[15] Alwayn IP, Xu Y, Basker M, Wu C, Buhler L, Lambrigts D, Treter S, Harper D, Kitamura H, Vitetta ES, Abraham S, Awwad M, White-Scharf ME, Sachs DH, Thall A, Cooper DK. Effects of specific anti-B and/or anti-plasma cell immunotherapy on antibody production in baboons: depletion of CD20-and CD22-positive B cells does not result in significantly decreased production of anti-alphaGal antibody. Xenotransplantation. 2001, 8(3): 157-171.
[16] Harper D, Gollackner B, Xu Y. Calderhead D, Ryan D, Li W, Cheng J, Wu C, Moran K. Latinne D. Bazin H, White-Scharf ME, Cooper DK, Awwad M. In vitro and in vivo investigation of a novel monoclonal antibody to plasma cells (W5 mAb). Xenotransplantation. 2004, 11(1): 78-90.
[17] Koma M, Miyagawa S, Honke K, Ikeda Y, Koyota S, Miyoshi S, Matsuda H, Tsuji S, Shirakura R, Taniguchi N. Reduction of the major xenoantigen on glycosphingolipids of swine endothelial cells by various glycosyltransferase. Glycobiology. 2000,10(7): 745-751.
[18] Ogawa H, Muramatsu H, Kobayashi T, Morozumi K, Yokoyama I, Kurosawa N, Nakao A, Muramatsu T. Molecular cloning of endo-beta-galactosidase C and its application in removing alpha-galactosyl xenoantigen from blood vessels in the pig kidney. J Biol Chem. 2000, 275(25): 19368-19374.
[19] Koma M, Miyagawa S, Honke K, Nakai R, Miyoshi S, Ohta M, Matsuda H, Shirakura R, Taniguchi N . The possibility of reducing xenoantigen levels with a novel Gal 3'-sulfotransferase. J Biochem. 2002, 131(4): 517-522
[20] Cowan PJ, Aminian A, Barlow H, Brown AA, Chen CG, Fisicaro N, Francis DM, Goodman DJ, Han W, Kurek M, Nottle MB, Pearse MJ, Salvaris E, Shinkel TA, Stainsby GV, Stewart AB, d'Apice AJ. Renal xenografts from triple-transgenic pigs are not hyperacutely rejected but cause coagulopathy in non-immunosuppressed baboons. Transplantation. 2000, 69(12): 2504-2515
[21] Mercier D, Charreau B, Wierinckx A, Keijser R, Adriaensens L, van den Berg R, Joziasse DH. Regulation of alpha1,3galactosyltransferase expression in pig endothelial cells. Implications for xenotransplantation . Eur J Biochem. 2002, 269(5): 1464-1473
[22] Ogawa H, Kobayashi I, Nagasaka T, Namil Y, Hayashi S, Kadomatsu K, Maramatsu T, Takagi H. Suppression of porcine xenoantigen expression by dominant-negative effect of α-1,3-galactosyltransferase (α-1,3-GT) splicing variants. Transplantation Proc. 2000, 32 (1): 58
[23] Parker W, Lin SS, Platt JL. Antigen expression in xenotransplantation :how low must it go ? Transplantation. 2001, 71 (2): 313 -319
[24] Phelps CJ, Koike C, Vaught TD, Boone J, Wells KD, Chen SH, Ball S, Specht SM, Polejaeva IA, Monahan JA, Jobst PM, Sharma SB, Lamborn AE, Garst AS, Moore M, Demetris AJ, Rudert WA, Bottino R, Bertera S, Trucco M, Starzl TE, Dai Y, Ayares DL. Production of alpha1,3-galactosyltransferase-deficient pigs. Science. 2003, 299(5605): 411-414.
[25] Kuwaki K, Tseng Y L, Dor F J. Heart transplantation in baboons usingalphal1,3-galactosyltransferase gene-knockout pigs as donors: initial experience. Nat Med. 2005,11(1): 29-31
[26] Yamada K, Yazawa K, Shimizu A. Marked prolongation of porcine renalxenograft survival in baboons through the use of alphal,3-galactosyltran- sferase gene-knockout donors and the cotransplantation of vascularized thymic tissue. Nat Med. 2005, 11(1): 32-34.
[27] Ramsoondar J J, Machaty Z, Costa C. Production of alpha1,3-galactosyl- transferaseknockout cloned pigs expressing humanalphal,2-fucosylosyltransf- erase. Biol Reprod. 2003, 69(2): 437-445.
[28] Ma YH , Zhou XG, Hu JH. Human xenoreactivity is reduced in micebearing porcine antisense alpha (1 ,3) galactosyltransferase c DNA.Acta Pharmacol Sin. 2001, 22 (3): 231-238.
[29] Yu L, Miao H, Guo L. Effect of RNA interference on Gal alpha 1,3 Gal expression in PIEC cells. DNA Cell Biol. 2005, 24(4): 235-243.
[30] Zhu M, Wang SS, Xia ZX, Cao RH, Chen D, Huang YB, Liu B, Chen ZK, Chen S. Inhibition of xenogeneic response in porcine endothelium using RNA interference. Transplantation. 2005, 79(3): 289-296.
[31] MacLaren L, Lee TD, Anderson D, Nass M, McAlister VC. Variation in porcine red blood cell alpha-galastosyl expression and agglutination by human serum. Transplant Proc. 1998, 30(5): 2468.
[32] Martin M, Muotri A, Gage F, Varki A. Human embryonic stem cells express an immunogenic nonhuman sialic acid. Nat Med. 2005, 11(2): 228-232.
[33] Zhu A, Hurst R. Anti-N-glycolylneuraminic acid antibodies identified in healthy human serum. Xenotransplantation. 2002, 9(6): 376-381.
[34] Tangvoranuntakul P, Gagneux P, Diaz S, Bardor M, Varki N, Varki A, Muchmore E. Human uptake and incorporation of an immunogenic nonhuman dietary sialic acid. Proc Natl Acad Sci USA. 2003, 100(21): 12045-12050.
[35] Oriol R, Barthod F, Bergemer AM, Ye Y, Koren E, Cooper DK. Monomorphic and polymorphic carbohydrate antigens on pig tissues: implications for organ xenotransplantatlon in the pig-to-human model. Transpl Int. 1994, 7(6): 405-413
[36] Zhu A. Binding of human natural antibodies to nonalphaGal xenoantigens on porcine erythrocytes. Transplantation. 2000, 69(11): 2422-2428..
[37] Chen G, Sun H, Yang H, Kubelik D, Garcia B, Luo Y, Xiang Y, Qian A, Copeman L, Liu W, Cardella CJ, Wang W, Xiong Y, Wall W, White DJ, Zhong R. The Role of Anti-non-Gal Antibodies in the Development of Acute Humoral Xenograft Rejection of hDAF Transgenic Porcine Kidneys in Baboons Receiving Anti-Gal Antibody Neutralization Therapy. Transplantation. 2006, 81(2): 273-283
[38] Gollackner B, Goh SK, Qawi I, Buhler L, Knosalla C, Daniel S, Kaczmarek E, Awwad M, Cooper DK, Robson SC. Acute vascular rejection of xenografts: roles of natural and elicited xenoreactive antibodies in activation of vascular endothelial cells and induction of procoagulant activity. Transplantation. 2004, 77(11): 1735-1741.
[39] Buhler L, Xu Y, Li W, Zhu A, Cooper DK. An investigation of the specificity of induced anti-pig antibodies in baboons. Xenotransplantation. 2003, 10(1): 88-93.
[40] Magre S, Takeuchi Y, Bartosch B. Xenotransplantation and pig endogenous retroviruses. Rev Med Virol. 2003, 13(5): 311-329.
[41] Irgang M, Sauer IM, Karlas A, Zeilinger K, Gerlach JC, Kurth R, Neuhaus P, Denner J. Porcine endogenous retroviruses: no infection in patients treated with a bioreactor based on porcine liver cells. J Clin Virol. 2003, 28(2): 141-154.
[42] Martin U, Tacke SJ, Simon AR, Schroder C, Wiebe K, Lapin B, Haverich A, Denner J, Steinhoff G. Absence of PERV specific humoral immune response in baboons after transplantation of porcine cells or organs. Transpl Int. 2002, 15(7): 361-368
[43] Korsgren O, Buhler LH, Groth CG. Toward clinical trials of islet xenotransplantation. Xenotransplantation. 2003, 10(4): 289-292.
[44] Karlas A, Kurth R, Denner J. Inhibition of porcine endogenous retroviruses by RNA interference: increasing the safety of xenotransplantation. Virology. 2004,325(1): 18-23.
[45] Mueller NJ, Kuwaki K, Dor FJ, Knosalla C, Gollackner B, Wilkinson RA, Sachs DH, Cooper DK, Fishman JA. Reduction of consumptive coagulopathy using porcine cytomegalovirus-free cardiac porcine grafts in pig-to-primate xenotransplantation. Transplantation. 2004, 78(10): 1449-1453.
[46] Mueller NJ, Livingston C, Knosalla C, Barth RN, Yamamoto S, Gollackner B, Dor FJ, Buhler L, Sachs DH, Yamada K, Cooper DK, Fishman JA. Activation of porcine cytomeg- alovirus,but not porcine lymphotropic herpesvirus, in pig-to-baboon xenotra- nsplantation. J Infect Dis. 2004, 189(9): 1628-1633.
[47] Goltz M, Ericsson T, Patience C, Huang CA, Noack S, Sachs DH, Ehlers B. Sequence analysis of the genome of porcine lymphotropic herpesvirus 1 and gene expression during posttransplant Lymphoproliferative disease of pigs. Virology. 2002, 294(2): 383-393.
[48] Huang CA, Fuchimoto Y, Gleit ZL, Ericsson T, Griesemer A, Scheier-Dolberg R, Melendy E, Kitamura H, Fishman JA, Ferry JA, Harris NL, Patience C, Sachs DH. Posttransplantation lymphoprolifer- ative disease in miniature swineafter allogeneic hematopoietic cell transplantation: similarity to human PTLD and association with a porcine gammaherpesvirus. Blood. 2001, 97(5): 1467-1473.
[49] Cho PS, Mueller NJ, Cameron AM, Cina RA, Coburn RC, Hettiaratchy S, Melendy E, Neville DM Jr, Patience C, Fishman JA, Sachs DH, Huang CA. Risk factors for the development of post-transplant lymphoproliferative disorder in a large animal model. Am J Transplant. 2004,4(8): 1274-1282.
[50] Ehlers B, Ulrich S, Goltz M. Detection of two novel porcine herpesviruses with high similarity to gammaherpesviruses. J Gen Virol. 1999, 80(4): 971-978.
[2] Saadi S, Platt JL. Immunology of xenotransplantation. Life Sci. 1998, 62 (5): 365-387.
[3] Ezzelarab M, Ayares D, Cooper DK. Carbohydrates in xenotransplantation. Immunol Cell Biol. 2005, 83(4): 396-404.
[4] Galili U, Shohet SB, Kobrin E, Stults CL, Macher BA. Man, apes, and Old World monkeys differ from other mammals in the expression of alpha-galactosyl epitopes on nucleated cells. J Biol Chem. 1988, 263(33): 17755-17762.
[5] Kobayashi T, Cooper DK. Anti-Gal, alpha-Gal epitopes, and xenotransplantation. Subcell Biochem. 1999, 32: 229-257.
[6] Dalmasso AP, Vercellotti GM, Fischel RJ, et al. Mechanism of complement activation in the hyperacute rejection of porcine organs transplanted into primate recipients. Am J Pathol. 1992, 140(5): 1157-1166.
[7] Cooper DK, Good AH, Koren E, Oriol R, Malcolm AJ, Ippolito RM, Neethling FA, Ye Y, Romano E. Identification of alpha-galactosyl and other carbohydrate epitopes that are bound by human anti-pig antibodies: relevance to discordant xenografting in man. Transpl Immunol. 1993, 1(3): 198-205
[8] Good AH, Cooper DK, Malcolm AJ, Ippolito RM, Koren E, Neethling FA, Ye Y, Zuhdi N, Lamontagne LR. Identification of carbohydrate structures that bind human antiporcine antibodies: implications for discordant xenografting in humans. Transplant Proc. 1992, 24(2): 559-562
[9] Milland J, Christiansen D, Sandrin MS. Alphal,3-galactosyltransferase knockout pigs are available for xenotransplantation: are glycosyltransferases still relevant?. Immunol Cell Biol. 2005, 83(6): 687-693.
[10] Lang J, Zhan J, Xu L, et al. Identification of peptide mimetics of xenoreactive α-Gal antigenic epitope by phage display. Biochem Biophys Res Commun. 2006, 344(1): 214-220.
[11] Neethling FA, Koren E, Ye Y, et al. Protection of pig kidney(PK15) cells by from the cytotoxic effect of anti-pig antibodies by α-galactosyl oligosaccharides. Transplantation. 1994, 57(6): 959-963
[12] Sandrin MS, Vaughan HA, Dabkowski PL, et al. Anti-pig IgM antibodies in human serum react predominantly with Gal(alpha 1-3)Gal epitopes. Proc Natl Acad Sci U S A. 1993,90(23): 11391-11395
[13] Evidence that intravenously administered alpha-galactosyl carbohydrates reduce baboon serum cytotoxicity to pig kidney cells (PK15) and transplanted pig hearts. Ye Y, Neethling FA, Niekrasz M, Koren E, Richards SV, Martin M, Kosanke S, Oriol R, Cooper DK. Transplantation. 1994, 58(3): 330-337.
[14] Manji RA, Manji JS, Koshal A, Korbutt GS, Rajotte RV. Human ABO blood group is important in survival and function of porcine working hearts. Am J Transplant. 2003, 3(3): 286-293
[15] Factors in xenograft rejection. Robson SC, Schulte am Esch J 2nd, Bach FH. Ann N Y Acad Sci. 1999, 875: 261-276.
[16] Lawson JH, Platt JL. Molecular barriers to xenotransplantation. Transplantation. 1996, 62(3): 303-310
[17] Koren E, Neethling FA, Richards S, Koscec M, Ye Y, Zuhdi N, Cooper DK. Binding and specificity of major immunoglobulin classes of preformed human anti-pig heart antibodies. Transpl Int. 1993, 6(6): 351-353.
[18] Roos A, Essers M, van Gijlswijk-Janssen D, Bovin NV, Daha MR. Both IgGand IgM anti-pig antibodies induce complement activation and cytotoxicity. Xenotransplantation. 2001, 8(1): 3-14
[19] Schaapherder AF, Daha MR, te Bulte MT, van der Woude FJ, Gooszen HG. Antibody-dependent cell-mediated cytotoxicity against porcine endothelium induced by a majority of human sera. Transplantation. 1994, 57(9): 1376-1382.
[20] Platt JL, Fischel RJ, Matas AJ, et al. Immunopathology of hyperacute xenograft rejection in a swine-to-primate model. Transplantation. 1991, 52(2): 214-220.
[1] Chen RH, Mitchell RN, Kadner A, Adams DH. Differential galactose alpha(1,3) galactose expression by porcine cardiac vascular endothelium. Xenotransplantation. 1999,6(3): 169-172.
[2] Zhu A, Hurst R. Anti-N-glycolylneuraminic acid antibodies identified in healthy human serum. Xenotransplantation. 2002, 9(6): 376-381.
[3] Manji RA, Manji JS, Koshal A, Korbutt GS, Rajotte RV. Human ABO blood group is important in survival and function of porcine working hearts. Am J Transplant. 2003, 3(3): 286-293.
[4] Leight GS, Kirkman R, Rasmusen BA, Rosenberg SA, Sachs DH, Terrill R, Williams GM. Transplantation in miniature swine. III: effects of MSLA and A-O blood group matching on skin allograft survival. Tissue Antigens. 1978 ,12(2):65-74.
[5] Rydberg L. ABO-incompatibility in solid organ transplantation. Transfus Med. 2001, 11(4): 325-342.
[6] Wu A, Buhler LH, Cooper DK. ABO-incompatible organ and bone marrow transplantation: current status. Transpl Int. 2003,16(5): 291-299.
[7] Rydberg L, Molne J, Strokan V, Svalander CT, Breimer ME. Histo-blood group A antigen expression in pig kidneys-implication for ABO incompatible pig-to-human xenotransplantation. Scand J Urol Nephrol. 2001, 35(1): 54-62.
[8] ANDRESEN E. Blood groups in pigs. Ann N Y Acad Sci. 1962, 97: 205-25.
[9] Gonzalez A, Friend M, Moreno A, Pintado CO, Vogeli P, Llanes D. A monoclonal antibody to swine erythrocytes recognizes the B blood group on the major glycophorin. Animal genetics. 1995, 26(5): 351-353.
[10] Phelps CJ, Koike C, Vaught TD, Boone J, Wells KD, Chen SH, Ball S, Specht SM, Polejaeva IA, Monahan JA, Jobst PM, Sharma SB, Lamborn AE, Garst AS, Moore M, Demetris AJ, Rudert WA, Bottino R, Bertera S, Trucco M, Starzl TE, Dai Y, Ayares DL. Production of alphal,3-galactosyltransferase -deficient pigs. Science. 2003, 299(5605): 411-414.
[11] Kuwaki K, Tseng YL, Dor FJ, Shimizu A, Houser SL, Sanderson TM, Lancos CJ, Prabharasuth DD, Cheng J, Moran K, Hisashi Y, Mueller N, Yamada K, Greenstein JL, Hawley RJ, Patience C, Awwad M, Fishman JA, Robson SC, Schuurman HJ, Sachs DH, Cooper DK. Heart transplantation in baboons using alphal,3-galactosyltransferase gene-knockout pigs as donors: initial experience. Nat Med. 2005, 11(1): 29-31.
[12] Yamada K, Yazawa K, Shimizu A, Iwanaga T, Hisashi Y, Nuhn M, O'Malley P, Nobori S, Vagefi PA, Patience C, Fishman J, Cooper DK, Hawley RJ, Greenstein J, Schuurman HJ, Awwad M, Sykes M, Sachs DH. Marked prolongation of porcine renal xenograft survival in baboons through the use of alphal,3-galactosyltransferase gene-knockout donors and the cotransplantation of vascularized thymic tissue. Nat Med. 2005, 11(1): 32-34.
[13] Hanagata G, Gasa S, Sako F, Makita A. Human blood group A and H glycolipids in porcine plasma. FEBS Lett. 1990, 261(2): 312-314.
[14] Makita A, Gasa S, Sako F, Hanagata G. Glycosphingolipids of porcine blood: human blood group A and H antigens with type 1 chain in erythrocytes and plasma. Indian J Biochem Biophys. 1990, 27(6): 402-410.
[15] Coombs RR, Goodwin RF. The blood groups of the pig. J Comp Pathol. 1956, 66(4): 317-331.
[1] Eto T, Ichikawa Y, Nishimura K, Ando S, Yamakawa T. Chemistry of lipid of the posthemyolytic residue or stroma of erythrocytes. ⅩⅤⅠ. Occurrence of ceramidepentasaccharide in the membrane of erythrocytes and reticulocytes of rabbit. J. Biochem. 1968, 64(2): 205-213.
[2] Kobayashi T, Cooper DK. Anti-Gal, alpha-Gal epitopes, and xenotransplantation. Subcell Biochem. 1999, 32: 229-257.
[3] Raymond H. Chen, Richard N. Mitchell, Alexander Kadner, David H. Adams. Differential galactose α(1, 3) galactose expression by porcine cardiac vascular endothelium. Xenotransplantation. 1999, 6(3): 169-172.
[4] 曾令宇，李幼平。猪到人异种移植超急性排斥反应的靶抗原。中国普外基与临床杂志．2003，10(4)：422-425．
[5] Manji RA, Manji JS. Koshal A, Korbutt GS, Rajotte RV. Human ABO bloodgroup is important in survival and function of porcine working hearts. Am J Transplant. 2003, 3(3): 286-293.
[6] Galili U, Shohet SB, Kobrin E, Stults CL, Macher BA. Man, apes, and Old World monkeys differ from other mammals in the expression of alpha-galactosyl epitopes on nucleated cells. J Biol Chem. 1988, 263(33): 17755-17762.
[7] Cooper DK, Good Aid, Koren E, Oriol R, Malcolm AJ, Ippolito RM, Neethling FA, Ye Y, Romano E. Zuhdi N. Identification of alpha-galactosyl and other carbohydrate epitopes that are bound by human anti-pig antibodies: relevance to discordant xenografting in man. Transpl Immunol. 1993, 1(3): 198-205.
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