Chapter 3 : The Complement System as a Hurdle to Xenotransplantation

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This chapter discusses the role of complement in the pathogenesis of tissue injury in xenograft rejection and reviews methods to inhibit complement activation as part of strategies to achieve xenograft survival. It begins with a brief overview of the complement system. The complement system is composed of 35 plasma and membrane-associated proteins, which include control proteins and receptors on cell membranes that recognize various fragments that result from complement activation. The membrane-associated complement regulators are of great interest to xenotransplantation. Although soluble complement inhibitors that can be used in vivo are beginning to be developed, small nontoxic molecules that inhibit complement efficiently are not yet available. Some of the large molecules that have been successful to abrogate hyperacute rejection (HAR) of the xenograft in experimental animals may be useful, at least temporarily, to reduce reperfusion injury and prevent HAR. A recent report indicates that a hexadecemeric multiple peptide of the C1q-binding site from human IgGi inhibits lysis of pig red cells by human serum, with an I value of 1 μM. This study suggests that peptides derived from the C1q binding region of immunoglobulins could hold promise to inhibit activation of the classical complement pathway.

Citation: Dalmasso A. 2001. The Complement System as a Hurdle to Xenotransplantation, p 55-83. In Platt J (ed), Xenotransplantation. ASM Press, Washington, DC. doi: 10.1128/9781555818043.ch3

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Complement System
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Figure 1

Schematic representation of the main pathways of complement activation. Mechanisms for activator recognition and initiation of activation are unique to each pathway. Classical pathway C3- and C5-convertases are also utilized by the lectin pathway. Sites of action of complement inhibitors are indicated by interrupted lines.

Citation: Dalmasso A. 2001. The Complement System as a Hurdle to Xenotransplantation, p 55-83. In Platt J (ed), Xenotransplantation. ASM Press, Washington, DC. doi: 10.1128/9781555818043.ch3
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1. Akami, T.,, R. Sawada,, N. Minato,, M. Naruto,, A. Yamada,, J. Imanishi,, M. Mitsuo,, I. Nakai,, M. Okamoto,, H. Nakajima,, K. Arakawa,, and T. Oka. 1992. Cytoprotective effect of CD59 antigen on xenotransplantation immunity. Transplant. Proc. 24:485487.
2. Alexandre, G. P. J.,, J. P. Squifflet,, M. De Bruyère,, D. Latinne,, R. Reding,, P. Gianello,, M. Carlier,, and Y. Pirson. 1987. Present experiences in a series of 26 ABO-incompatible living donor renal allografts. Transplant. Proc. 19:4538542.
3. Alwayn, I. P. J.,, M. Basker,, L. Buhler,, and D. K. C. Cooper. 1999. The problem of anti-pig antibodies in pig-to-primate xenografting: current and novel methods of depletion and/or suppression of production of anti-pig antibodies. Xenotransplantation 6:157168.
4. Atkinson, J. P.,, T. J. Oglesby,, D. White,, E. A. Adams,, and M. K. Liszewski. 1991. Separation of self from non-self in the complement system: a role for membrane cofactor protein and decay accelerating factor. Clin. Exp. Immunol. 86(S1):2730.
5. Azimzadeh, A.,, P. Wolf,, A. P. Dalmasso,, M. Odeh,, J. P. Beller,, M. Fabre,, B. Charreau,, K. Thibaudeau,, J. Cinqualbre,, J. P. Soulillou,, and I. Anegon. 1996. Assessment of hyperacute rejection in a rat-to-primate cardiac xenograft model. Transplantation 61:13051313.
6. Bach, F. H.,, C. Ferran,, P. Hechenlettner,, W. Mark,, N. Koyamada,, T. Miyatake,, H. Winkler,, A. Badrichani,, D. Candinas,, and W. W. Hancock. 1997. Accommodation of vascularized xenografts: expression of "protective genes" by donor endothelial cells in a host TH2 cytokine environment. Nature Med. 3:196204.
7. Bach, F. H.,, M. A. Turman,, G. M. Vercellotti,, J. L. Platt,, and A. P. Dalmasso. 1991. Accommodation: a working paradigm for progressing toward clinical discordant xenografting. Transplant. Proc. 23:205207.
8. Bannett, A. D.,, R. F. McAlack,, M. Morris,, M. W. Chopek,, and J. L. Platt. 1989. ABO incompatible renal transplantation: a qualitative analysis of native endothelial tissue ABO antigens after transplantation. Transplant. Proc. 21:783785.
9. Basta, M.,, L. F. Fries,, and M. M. Frank. 1991. High doses of intravenous Ig inhibit in vitro uptake of C4 fragments onto sensitized erythrocytes. Blood 77:376380.
10. Benzaquen, L. R.,, A. Nicholson-Weller,, and J. A. Halperin. 1994. Terminal complement proteins C5b-9 release basic fibroblast growth factor and platelet-derived growth factor from endothelial cells. J. Exp. Med. 179:985992.
11. Biesecker, G.,, L. Dihel,, K. Enney,, and R. A. Bendele. 1999. Derivation of RNA aptamer inhibitors of human complement C5. lmmunopharmacology 42:219230.
12. Blakely, M. L.,, W. J. Van der Werf,, M. C. Berndt,, A. P. Dalmasso,, F. H. Bach,, and W. W. Hancock. 1994. Activation of intragraft endothelial and mononuclear cells during discordant xenograft rejection. Transplantation 58:10591066.
13. Botto, M.,, C. Dell'Agnola,, A. E. Bygrave,, E. M. Thompson,, H. T. Cook,, F. Petry,, M. Loos,, P. P. Pandolfi,, and M. J. Walport. 1998. Homozygous Clq deficiency causes glomerulonephritis associated with multiple apoptotic bodies. Nature Genet. 19:5659.
14. Brauer, R. B.,, W. M. I. Baldwin,, M. R. Daha,, S. K. Pruitt,, and F. Sanfilippo. 1993. Use of C6-deficient rats to evaluate the mechanism of hyperacute rejection of discordant cardiac xenografts. J. Immunol. 151:72407248.
15. Buerke, M.,, D. Prufer,, M. Dahm,, H. Oelert,, J. Meyer,, and H. Darius. 1998. Blocking of classical complement pathway inhibits endothelial adhesion molecule expression and preserves ischemic myocardium from reperfusion injury. J. Pharmacol. Exp. Ther. 286:429438.
16. Bustos, M.,, T. M. Coffman,, S. Saadi,, and J. L. Platt. 1997. Modulation of eicosanoid metabolism in endothelial cells in a xenograft model. Role of cyclooxygenase-2. J. Clin. Invest. 100:11501158.
17. Byrne, G. W.,, K. R. McCurry,, D. Kagan,, C. Quinn,, M. J. Martin,, J. L. Platt,, and J. S. Logan. 1995. Protection of xenogeneic cardiac endothelium from human complement by expression of CD59 or DAF in transgenic mice. Transplantation 60:11491156.
18. Byrne, G. W.,, K. R. McCurry,, M. J. Martin,, S. M. McClellan,, J. L. Platt,, and J. S. Logan. 1997. Transgenic pigs expressing human CD59 and decay-accelerating factor produce an intrinsic barrier to complement-mediated damage. Transplantation 63:149155.
19. Charreau, B.,, A. Cassard,, L. Tesson,, B. Le Mauff,, J. M. Navenot,, D. Blanchard,, D. Lublin,, J. P. Soulillou,, and I. Anegon. 1994. Protection of rat endothelial cells from primate complement-mediated lysis by expression of human CD59 and/or decay-accelerating factor. Transplantation 58:12221229.
20. Chartrand, C.,, S. O'Regan,, P. Robitaille,, and M. Pinto-Blonde. 1979. Delayed rejection of cardiac xenografts in C6-deficient rabbits. Immunology 38:245248.
21. Christiansen, D.,, J. Milland,, B. R. Thorley,, I. F. McKenzie,, and B. E. Loveland. 1996. A functional analysis of recombinant soluble CD46 in vivo and a comparison with recombinant soluble forms of CD55 and CD35 in vitro. Eur. J. Immunol. 26:578585.
22. Christiansen, D.,, J. Milland,, B. R. Thorley,, I. F. McKenzie,, P. L. Mottram,, L. J. Purcell,, and B. E. Loveland. 1996. Engineering of recombinant soluble CD46: an inhibitor of complement activation. Immunology 87:348354.
23. Cooper, N. R. 1985. The classical complement pathway: activation and regulation of the first complement component. Adv. Immunol. 37:151216.
24. Costa, C.,, L. Zhao,, S. Decesare,, and W. L. Fodor. 1999. Comparative analysis of three genetic modifications designed to inhibit human serum-mediated cytolysis. Xenotransplantation 6:616.
25. Cowan, P. J.,, C. G. Chen,, T. A. Shinkel,, N. Fisicaro,, E. Salvaris,, A. Aminian,, M. Romanella,, M. J. Pearse,, and A. J. d'Apice. 1998. Knock out of alphal,3-galactosyltransferase or expression of alphal,2-fucosyltransferase further protects CD55- and CD59-expressing mouse hearts in an ex vivo model of xenograft rejection. Transplantation 65:15991604.
26. Cowan, P. J.,, T. A. Shinkel,, A. Aminian,, M. Romanella,, P. L. Wigley,, A. J. Lome,, M. B. Nottle,, M. J. Pearse,, and A. J. d'Apice. 1998. High-level co-expression of complement regulators on vascular endothelium in transgenic mice: CD55 and CD59 provide greater protection from human complement-mediated injury than CD59 alone. Xenotransplantation 5:184190.
27. Cowan, P. J.,, C. A. Somerville,, T. A. Shinkel,, M. Katerelos,, A. Aminian,, M. Romanella,, M. J. Tange,, M. J. Pearse,, and A. J. d'Apice. 1998. High-level endothelial expression of human CD59 prolongs heart function in an ex vivo model of xenograft rejection. Transplantation 65:826831.
28. Cowan, P. J.,, D. Tsang,, C. M. Pedic,, L. R. Abbott,, T. A. Shinkel,, A. J. d'Apice,, and M. J. Pearse. 1998. The human ICAM-2 promoter is endothelial cell-specific in vitro and in vivo and contains critical Spl and GATA binding sites. J. Biol. Chem. 273:1173711744.
29. Cozzi, E.,, A. W. Tucker,, G. A. Langford,, G. Pino-Chavez,, L. Wright,, M. J. O'Connell,, V. J. Young,, R. Lancaster,, M. McLaughlin,, K. Hunt,, M. C. Bordin,, and D. J. White. 1997. Characterization of pigs transgenic for human decay-accelerating factor. Transplantation 64:13831392.
30. Cozzi, E.,, N. Yannoutsos,, G. A. Langford,, G. Pino-Chavez,, J. Wallwork,, and D. J. G. White,. 1997. Effect of transgenic expression of human decay-accelerating factor on the inhibition of hyperacute rejection of pig organs, p. 665682. In D. K. C. Cooper,, E. Kemp,, J. L. Platt,, and D. J. G. White (ed.), Xenotransplantation. The Transplantation of Organs and Tissues Between Species, 2nd ed. Springer-Verlag, Berlin, Germany.
31. Daggett, C. W.,, M. Yeatman,, A. J. Lodge,, E. P. Chen,, P. Van Trigt,, G. W. Byrne,, J. S. Logan,, J. H. Lawson,, J. L. Platt,, and R. D. Davis. 1997. Swine lungs expressing human complement-regulatory proteins are protected against acute pulmonary dysfunction in a human plasma perfusion model. J. Thoracic Cardiovasc. Surg. 113:390398.
32. Dalmasso, A. P. 1986. Complement in the pathophysiology and diagnosis of human diseases. Crit. Rev. Clin. Lab. Sci. 24:123183.
33. Dalmasso, A. P. 1992. The complement system in xenotransplantation. Immunopharmacology 24:149160.
34. Dalmasso, A. P., 1997. Role of complement in xenograft rejection, p. 3860. In D. K. C. Cooper,, E. Kemp,, J. L. Platt,, and D. J. G. White (ed.), Xenotransplantation. The Transplantation of Organs and Tissues Between Species, 2nd ed. Springer-Verlag, Berlin, Germany.
35. Dalmasso, A. P.,, and B. A. Benson,. 1988. Pore size of lesions induced by complement on red cell membranes and its relation to C5b-8, C5b-9 and poly C9, p. 207219. In E. R. Podack (ed.), Cytolytic Lymphocytes and Complement: Effectors of the Immune System, vol. 1. CRC Press, Boca Raton, Fla.
36. Dalmasso, A. P.,, B. A. Benson,, J. S. Johnson,, C. Larcto,, and M. Abrahamsen. 2000. Resistance against the membrane attack complex of complement induced in porcine endothelial cells with a Galα(l-3) Gal binding lectin: up-regulation of CD59 expression. J. Immunol. 164:37643773.
37. Dalmasso, A. P.,, T. He,, and B. A. Benson. 1996. Human IgM xenoreactive natural antibodies can induce resistance of porcine endothelial cells to complement-mediated injury. Xenotransplantation 3:5462.
38. Dalmasso, A. P.,, and J. L. Platt. 1994. Potentiation of C1 inhibitor plus heparin in prevention of complement-mediated activation of endothelial cells in a model of xenograft hyperacute rejection. Transplant. Proc. 26:12461247.
39. Dalmasso, A. P.,, and J. L. Platt. 1993. Prevention of complement-mediated activation of xenogeneic endothelial cells in an in vitro model of xenograft hyperacute rejection by C1 inhibitor. Transplantation 56:11711176.
40. Dalmasso, A. P.,, G. M. Vercellotti,, R. J. Fischel,, R. M. Bolman,, F. H. Bach,, and J. L. Platt. 1992. Mechanism of complement activation in the hyperacute rejection of porcine organs transplanted into primate recipients. Am. J. Pathol. 140:11571166.
41. Dalmasso, A. P.,, G. M. Vercellotti,, J. L. Platt,, and F. H. Bach. 1991. Inhibition of complement-mediated endothelial cell cytotoxicity by decay accelerating factor. Potential for prevention of xenograft hyperacute rejection. Transplantation 52:530533.
42. Davis, A. E. 1988. C1 inhibitor and hereditary angioneurotic edema. Annu. Rev. Immunol. 6:595628.
43. Davis, E. A.,, T. T. Lam,, Z. Qian,, S. Ibrahim,, W. M. Baldwin, 3rd, and F. P. Sanfilippo. 1995. Inhibition of neutrophil adhesion and the membrane attack complex of complement synergistically prolongs cardiac xenograft survival. J. Heart Lung Transplant. 14:973980.
44. Dorling, A.,, C. Stocker,, T. Tsao,, D. O. Haskard,, and R. I. Lechler. 1996. In vitro accommodation of immortalized porcine endothelial cells: resistance to complement mediated lysis and down-regulation of VCAM expression induced by low concentrations of polyclonal human IgG antipig antibodies. Transplantation 62:11271136.
45. Fearon, D. T.,, and R. H. Carter. 1995. The CD 19/CR2/TAPA-1 complex of B lymphocytes: linking natural to acquired immunity. Annu. Rev. Immunol. 13:127149.
46. Fiane, A. E.,, T. E. Mollnes,, V. Videm,, T. Hovig,, K. Høågasen,, O. J. Melbye,, L. Spruce,, W. T. Moore,, A. Sahu,, and J. D. Lambris. 1999. Compstatin, a peptide inhibitor of C3, prolongs survival of ex vivo perfused pig xenografts. Xenotransplantation 6:5265.
47. Fiane, A. E.,, V. Videm,, H. T. Johansen,, O. J. Mellbye,, E. W. Nielsen,, and T. E. Mollnes. 1999. C1-inhibitor attenuates hyperacute rejection and inhibits complement, leukocyte and platelet activation in an ex vivo pig-to-human perfusion model. Immunopharmacology 42:231243.
48. Fodor, W. L.,, S. A. Rollins,, E. R. Guilmette,, E. Setter,, and S. P. Squinto. 1995. A novel bifunctional chimeric complement inhibitor that regulates C3 convertase and formation of the membrane attack complex. J. Immunol. 155:41354138.
49. Fodor, W. L.,, B. L. Williams,, L. A. Matis,, J. A. Madri,, S. A. Rollins,, J. W. Knight,, W. Velander,, and S. P. Squinto. 1994. Expression of a functional human complement inhibitor in a transgenic pig as a model for the prevention of xenogeneic hyperacute organ rejection. Proc. Natl. Acad. Sci. USA 91:1115311157.
50. Foreman, K. E.,, M. M. Glovsky,, R. L. Warner,, S. J. Horvath,, and P. A. Ward. 1996. Comparative effect of C3a and C5a on adhesion molecule expression on neutrophils and endothelial cells. Inflammation 20:19.
51. Friedl, H. P.,, G. O. Till,, U. S. Ryan,, and P. A. Ward. 1989. Mediator-induced activation of xanthine oxidase in endothelial cells. FASEBJ. 3:25122518.
52. Fryer, J.,, J. R. Leventhal,, A. P. Dalmasso,, P. Simone,, S. Chen,, L. H. Sun,, J. Jesserun,, N. Reinsmoen,, and A. Matas. 1994. Cellular rejection in a discordant xenograft when hyperacute rejection is prevented: analysis using adoptive and passive transfer. Transplant Immunol. 2:8793.
53. Fryer, J. P.,, J. R. Leventhal,, A. P. Dalmasso,, S. Chen,, P. A. Simone,, J. J. Goswitz,, N. L. Reinsmoen,, and A. J. Matas. 1995. Beyond hyperacute rejection. Accelerated rejection in a discordant xenograft model by adoptive transfer of specific cell subsets. Transplantation 59:171176.
54. Gambiez, L.,, B. J. Weill,, C. Chereau,, Y. Calmus,, and D. Houssin. 1990. The hyperacute rejection of guinea pig to rat heart xenografts is mediated by preformed IgM. Transplant. Proc. 22:1058.
55. Gautreau, C.,, T. Kojima,, G. Woimant,, J. Cardoso,, P. Devillier,, and D. Houssin. 1995. Use of intravenous immunoglobulin to delay xenogeneic hyperacute rejection. An in vivo and in vitro evaluation. Transplantation 60:903907.
56. Gewurz, H.,, D. S. Clark,, M. D. Cooper,, R. L. Varco,, and R. A. Good. 1967. Effect of cobra venom-induced inhibition of complement activity on allograft and xenograft rejection reactions. Transplantation 5:12961303.
57. Good, A. H.,, D. K. C. Cooper,, A. J. Malcolm,, R. M. Ippolito,, E. Koren,, F. A. Neethling,, Y. Ye,, N. Zuhdi,, and L. R. Lamontagne. 1992. Identification of carbohydrate structures that bind human antiporcine antibodies: implications for discordant xenografting in humans. Transplant. Proc. 24:559562.
58. Guo, W. X.,, B. Ghebrehiwet,, B. Weksler,, K. Schweitzer,, and E. I. Peerschke. 1999. Up-regulation of endothelial cell binding proteins/receptors for complement component C1q by inflammatory cytokines. J. Lab. Clin. Med. 133:541550.
59. Hamilton, K. K.,, R. Hattori,, C. T. Esmon,, and P. J. Sims. 1990. Complement proteins C5b-9 induce vesiculation of the endothelial plasma membrane and expose catalytic surface for assembly of the prothrombinase enzyme complex. J. Biol. Chem. 265:38093814.
60. Hasan, R.,, J. Van den Bogaerde,, J. Forty,, L. Wright,, J. Wallwork,, and D. J. G. White. 1992. Xenograft adaptation is dependent on the presence of antispecies antibody, not prolonged residence in the recipient. Transplant. Proc. 24:531532.
61. Hattori, R.,, K. K. Hamilton,, R. P. McEver,, and P. J. Sims. 1989. Complement proteins C5b-9 induce secretion of high molecular weight multimers of endothelial von Willebrand factor and translocation of granule membrane protein GMP-140 to the cell surface. J. Biol. Chem. 264:90539060.
62. Haviland, D. L.,, R. L. McCoy,, W. T. Whitehead,, H. Akama,, E. P. Molmenti,, A. Brown,, J. C. Haviland,, W. C. Parks,, D. H. Perlmutter,, and R. A. Wetsel. 1995. Cellular expression of the C5a anaphylatoxin receptor (C5aR): demonstration of C5aR on nonmyeloid cells of the liver and lung. J. Immunol. 154:18611869.
63. Higgins, P. J.,, J. L. Ko,, R. Lobell,, C. Sardonini,, M. K. Alessi,, and C. G. Yeh. 1997. A soluble chimeric complement inhibitory protein that possesses both decay-accelerating and factor I cofactor activities. J. Immunol. 158:28722881.
64. Hinchliffe, S. J.,, N. K. Rushmere,, S. M. Hanna,, and B. P. Morgan. 1998. Molecular cloning and functional characterization of the pig analogue of CD59: relevance to xenotransplantation. J. Immunol. 160:39243932.
65. Hourcade, D.,, V. M. Holers,, and J. P. Atkinson. 1989. The regulators of complement activation (RCA) gene cluster. Adv. Immunol. 45:381416.
66. Huang, J.,, L. J. Kim,, R. Mealey,, H. C. Marsh,, Y. Zhang,, A. J. Tenner,, E. S. Connolly,, and D. J. Pinsky. 1999. Neuronal protection in stroke by an sLex-glycosylated complement inhibitory protein. Science 285:595599.
67. Ierino, F. L.,, T. Kozlowski,, J. B. Siegel,, A. Shimizu,, R. B. Colvin,, P. T. Banerjee,, D. K. Cooper,, A. B. Cosimi,, F. H. Bach,, D. H. Sachs,, and S. C. Robson. 1998. Disseminated intravascular coagulation in association with the delayed rejection of pig-to-baboon renal xenografts. Transplantation 66:14391450.
68. Dircke, N. S.,, and J. L. Platt. 1996. Shedding of heparan sulfate proteoglycan by stimulated endothelial cells: evidence for proteolysis of cell-surface molecules. J. Cell. Physiol. 168:625637.
69. Ikeda, K.,, K. Nagasawa,, T. Horiuchi,, T. Tsuru,, H. Nishizaka,, and Y. Niho. 1997. C5a induces tissue factor activity on endothelial cells. Thromb. Haemost. 77:394398.
70. Jefferson, K. P.,, K. S. Tyerman,, M. McLeish,, D. S. J. CoUier,, and S. Thiru. 1991. Donor pretreatment prolongs survival of discordant xenografts. Transplant. Proc. 23:22802281.
71. Johnson, E. M.,, J. Leventhal,, A. P. Dalmasso,, J. Goswitz,, P. Simone,, S. Chen,, M. Moyle,, and A. J. Matas. 1996. Inactivation of C3 and C5 prolongs cardiac xenograft survival and decreases leukocyte infiltration in a model of delayed xenograft rejection. Transplant. Proc. 28:603.
72. Johnson, E. M.,, J. Leventhal,, A. P. Dalmasso,, J. Goswitz,, P. Simone,, S. Chen,, M. Moyle,, and A. J. Matas. 1996. Use of a novel CD1lb/CD18 inhibitory agent in a C6 deficient rat to evaluate delayed xenograft rejection. Transplant. Proc. 28:728.
73. Johnston, P. S.,, S. M. L. Lim,, M. W. Wang,, L. Wright,, and D. J. G. White. 1991. Hyperacute rejection of xenografts in the complete absence of antibody. Transplant. Proc. 23:877879.
74. Kerr, S. R.,, A. P. Dalmasso,, E. V. Apasova,, S. S. Chen,, M. Kirschfink,, and A. J. Matas. 1999. Mouse-to-rabbit xenotransplantation: a new small animal model of hyperacute rejection mediated by the classical complement pathway. Transplantation 67:360365.
75. Kilgore, K. S.,, C. M. Flory,, B. F. Miller,, V. M. Evans,, and J. S. Warren. 1996. The membrane attack complex of complement induces interleukin-8 and monocyte chemoattractant protein-1 secretion from human umbilical vein endothelial cells. Am. J. Pathol. 149:953961.
76. Kishore, U.,, M. V. Perdikoulis,, P. Strong,, and K. B. M. Reid. 1998. A homotrimer of the B-chain globular head region of C1q is an inhibitor of Clq-mediated complement activation. Mol. Immunol. 35:375.
77. Kojima, T.,, C. A. Del Carpio,, H. Tajiri,, K. Yoshikawa,, S. Saga,, and I. Yokoyama. 1999. Inhibition of complement-mediated immune hemolysis by peptides derived from the constant domain of immunoglobulin. Transplantation 67:637638.
78. Korb, L. C.,, and J. M. Ahearn. 1997. C1q binds directly and specifically to surface blebs of apoptotic human keratinocytes: complement deficiency and systemic lupus erythematosus revisited. J. Immunol. 158:45254528.
79. Kroshus, T. J.,, R. M. Bolman,, A. P. Dalmasso,, S. A. Rollins,, E. R. Guilmette,, B. L. Williams,, S. P. Squinto,, and W. L. Fodor. 1996. Expression of human CD59 in transgenic pig organs enhances organ survival in an ex vivo xenogeneic perfusion model. Transplantation 61:15131521.
80. Kroshus, T. J.,, S. A. Rollins,, A. P. Dalmasso,, E. A. Elliot,, L. A. Matis,, S. P. Squinto,, and R. M. Bolman. 1995. Complement inhibition with an anti-C5 monoclonal antibody prevents acute cardiac tissue injury in an ex vivo model of pig-to-human xenotransplantation. Transplantation 60:11941202.
81. Kroshus, T. J.,, C. T. Salerno,, C. G. Yeh,, P. J. Higgins,, R. M. Bolman,, and A. P. Dalmasso. 2000. A recombinant soluble chimeric complement inhibitor composed of human CD46 and CD55 reduces acute cardiac tissue injury in models of pig-to-human heart transplantation. Transplantation 69:22822289.
82. Lambrigts, D.,, D. H. Sachs,, and D. K. Cooper. 1998. Discordant organ xenotransplantation in primates: world experience and current status. Transplantation 66:547561.
83. Latremouille, C.,, N. Haeffner-Cavaillon,, N. Goussef,, C. Mandet,, N. Hinglais,, P. Bruneval,, J. Bariety,, A. Carpentier,, and D. Glotz. 1994. Normal human polyclonal immunoglobulins for intravenous use significantly delay hyperacute xenograft rejection. Transplant. Proc. 26:1285.
84. Leventhal, J. R.,, A. P. Dalmasso,, J. W. Cromwell,, J. L. Platt,, C. J. Manivel,, R. M. Bolman,, and A. J. Matas. 1993. Prolongation of cardiac xenograft survival by depletion of complement. Transplantation 55:857865.
85. Leventhal, J. R.,, A. J. Matas,, L. H. Sun,, S. Reif,, R. M. Bolman,, A. P. Dalmasso,, and J. L. Platt. 1993. The immunopathology of cardiac xenograft rejection in the guinea pig-to-rat model. Transplantation 56:18.
86. Leventhal, J. R.,, P. Sakiyalak,, J. Witson,, P. Simone,, A. J. Matas,, R. M. Bolman,, and A. P. Dalmasso. 1994. The synergistic effect of combined antibody and complement depletion on discordant cardiac xenograft survival in nonhuman primates. Transplantation 57:974978.
87. Lin, S. S.,, B. C. Weidner,, G. W. Byrne,, L. E. Diamond,, J. H. Lawson,, C. W. Hoopes,, L. J. Daniels,, C. W. Daggett,, W. Parker,, R. C. Harland,, R. D. Davis,, R. R. Bollinger,, J. S. Logan,, and J. L. Platt. 1998. The role of antibodies in acute vascular rejection of pig-to-baboon cardiac transplants. J. Clin. Invest. 101:17451756.
88. Lozada, C.,, R. I. Levin,, M. Huie,, R. Hirschhorn,, D. Naime,, M. Whitlow,, P. A. Recht,, B. Golden,, and B. N. Cronstein. 1995. Identification of Clq as the heat-labile serum cofactor required for immune complexes to stimulate endothelial expression of the adhesion molecules E-selectin and intercellular and vascular cell adhesion molecules 1. Proc. Natl. Acad. Sci. USA 92:83788382.
89. Magee, J. C.,, B. H. Collins,, R. C. Harland,, B. J. Lindman,, R. R. Bollinger,, M. M. Frank,, and J. L. Platt. 1995. Immunoglobulin prevents complement-mediated hyperacute rejection in swine-to-primate xenotransplantation. J. Clin. Invest. 96:24042412.
90. Maher, S. E.,, D. L. Pflugh,, N. J. Larsen,, M. F. Rothschild,, and A. L. Bothwell. 1998. Structure/function characterization of porcine CD59: expression, chromosomal mapping, complement-inhibition, and co-stimulatory activity. Transplantation 66:10941100.
91. Makrides, S. C. 1998. Therapeutic inhibition of the complement system. Pharmacol. Rev. 50:5987.
92. Matis, L. A.,, and S. A. Rollins. 1995. Complement-specific antibodies: designing novel anti-inflammatories. Nat. Med. 1:839841.
93. Matsushita, M. 1996. The lectin pathway of the complement system. Microbiol. Immunol. 40:887893.
94. McCurry, K. R.,, D. L. Kooyman,, C. G. Alvarado,, A. H. Cotterell,, M. J. Martin,, J. S. Logan,, and J. L. Platt. 1995. Human complement regulatory proteins protect swine-to-primate cardiac xenografts from humoral injury. Nat. Med. 1:423427.
95. McCurry, K. R.,, D. L. Kooyman,, L. E. Diamond,, G. W. Byrne,, J. S. Logan,, and J. L. Platt. 1995. Transgenic expression of human complement regulatory proteins in mice results in diminished complement deposition during organ xenoperfusion. Transplantation 59:11771182.
96. Meri, S. 1994. Protectin (CD59). Complement lysis inhibitor and prototype domain in a new protein super-family. Immunologist 2:149155.
97. Mikata, S.,, S. Miyagawa,, K. Iwata,, S. Nagasawa,, M. Hatanaka,, M. Matsumoto,, W. Kamiike,, H. Matsuda,, R. Shirakura,, and T. Seya. 1998. Regulation of complement-mediated swine endothelial cell lysis by a surface-bound form of human C4b binding protein. Transplantation 65:363368.
98. Miyagawa, S.,, H. Hirose,, R. Shirakura,, Y. Naka,, S. Nakata,, Y. Kawashima,, T. Seya,, M. Matsumoto,, A. Uenaka,, and H. Kitamura. 1988. The mechanism of discordant xenograft rejection. Transplantation 46:825830.
99. Moran, P.,, H. Beasley,, A. Gorrell,, E. Martin,, P. Gribling,, H. Fuchs,, N. Gillett,, L. E. Burton,, and I. W. Caras. 1992. Human recombinant soluble decay accelerating factor inhibits complement activation in vitro and in vivo. J. Immunol. 149:17361743.
100. Morgan, B. P., 1993. Cellular responses to the membrane attack complex, p. 325351. In K. Whaley,, M. Loos,, and J. M. Weiler (ed.), Complement in Health and Disease, vol. 20. Kluwer Academic Publishers, Boston, Mass.
101. Morgan, B. P. 1995. Physiology and pathophysiology of complement: progress and trends. Crit. Rev. Clin. Lab. Sci. 32:265298.
102. Mulder, L. C. F.,, M. Mora,, M. Lazzeri,, M. Boschi,, E. Ciccopiedi,, C. Melli,, P. Bruzzone,, D. Alfani,, R. Cortesini,, and M. Rossini. 1996. Human MCP and DAF double transgenic mice are protected from human complement attack in an in vivo model. Transplant. Proc. 28:589.
103. Müller-Eberhard, H. J., 1992. Complement: chemistry and pathways, p. 3361. In J. I. Gallin,, I. M. Goldstein,, and R. Snyderman (ed.), Inflammation. Basic Principles and Clinical Correlates. Raven Press, New York, N.Y.
104. Murphy, H. S.,, J. A. Shayman,, G. O. Till,, M. Mahrougui,, C. B. Owens,, U. S. Ryan,, and P. A. Ward. 1992. Superoxide responses of endothelial cells to C5a and TNF-alpha: divergent signal transduction pathways. Am. J. Physiol. 263:L5159.
105. Nelson, R. A. 1966. A new concept of immunosuppression in the hypersensitivity reactions and in transplantation immunity. Surv. Ophthalmol. 11:498505.
106. Nicholson-Weller, A.,, and J. A. Halperin. 1993. Membrane signaling by complement C5b-9, the membrane attack complex. Immunol. Res. 12:244257.
107. Nicholson-Weller, A.,, and C. Wang. 1994. Structure and function of decay accelerating factor CD55. J. Lab. Clin. Med. 123:485491.
108. Oglesby, T. J.,, C. J. Allen,, M. K. Liszewski,, D. J. G. White,, and J. P. Atkinson. 1992. Membrane cofactor protein (CD46) protects cells from complement-mediated attack by an intrinsic mechanism. J. Exp. Med. 175:15471551.
109. Osman, N.,, I. F. McKenzie,, K. Ostenried,, Y. A. Ioannou,, R. J. Desnick,, and M. S. Sandrin. 1997. Combined transgenic expression of α-galactosidase and αl,2-fucosyltransferase leads to optimal reduction in the major xenoepitope Galα(l,3)Gal. Proc. Natl. Acad. Sci. USA 94:1467714682.
110. Owen, C. A.,, M. A. Campbell,, P. L. Sannes,, S. S. Boukedes,, and E. J. Campbell. 1995. Cell surface-bound elastase and cathepsin G on human neutrophils: a novel, non-oxidative mechanism by which neutrophils focus and preserve catalytic activity of serine proteinases. J. Cell Biol. 131:775789.
111. Oxvig, C.,, C. Lu,, and T. A. Springer. 1999. Conformational changes in tertiary structure near the ligand binding site of an integrin I domain. Proc. Natl. Acad. Sci. USA 96:22152220.
112. Pangburn, M. K.,, and H. J. Miiller-Eberhard. 1984. The alternative pathway of complement. Springer Semin. Immunopathol. 7:163203.
113. Pascual, M.,, and L. E. French. 1995. Complement in human diseases: looking towards the 21st century. Immunol. Today 16:5861.
114. Peerschke, E. I.,, K. B. Reid,, and B. Ghebrehiwet 1993. Platelet activation by Clq results in the induction of αIIb/β3 integrins (GPIIb-IIIa) and the expression of P-selectin and procoagulant activity. J. Exp. Med. 178:579587.
115. Pierre, A. F.,, A. M. Xavier,, M. Liu,, S. D. Cassivi,, T. F. Lindsay,, H. C. Marsh,, A. S. Slutsky,, and S. H. Keshavjee. 1998. Effect of complement inhibition with soluble complement receptor 1 on pig allotransplant lung function. Transplantation 66:723732.
116. Platt, J. L.,, A. P. Dalmasso,, B. J. Lindman,, N. S. Dircke,, and F. H. Bach. 1991. The role of C5a and antibody in the release of heparan sulfate from endothelial cells. Eur. J. Immunol. 21:28872890.
117. Platt, J. L.,, G. M. Vercellotti,, A. P. Dalmasso,, A. J. Matas,, R. M. Bolman,, J. S. Najarian,, and F. H. Bach. 1990. Transplantation of discordant xenografts: a review of progress. Immunol. Today 11:450456.
118. Platt, J. L.,, G. M. Vercellotti,, B. Lindman,, T. R. OegemaJr.,, F. H. Bach,, and A. P. Dalmasso. 1990. Release of heparan sulfate from endothelial cells: implications for pathogenesis of hyperacute rejection. J. Exp. Med. 171:13631368.
119. Pruitt, S. K.,, W. M. Baldwin,, H. C. MarshJr.,, S. S. Lin,, C. G. Yeh,, and R. R. Bollinger. 1991. The effect of soluble complement receptor type 1 on hyperacute xenograft rejection. Transplantation 52:868873.
120. Pruitt, S. K.,, R. R. Bollinger,, B. H. Collins,, H. C. MarshJr.,, J. L. Levin,, A. R. Rudolph,, W. M. Baldwin, 3rd,, and F. Sanfilippo. 1997. Effect of continuous complement inhibition using soluble complement receptor type 1 on survival of pig-to-primate cardiac xenografts. Transplantation 63:900902.
121. Pruitt, S. K.,, A. D. Kirk,, R. R. Bollinger,, H. C. MarshJr.,, B. H. Collins,, J. L. Levin,, J. R. Mault,, J. S. Heinle,, S. Ibrahim,, A. R. Rudolph,, W. M. Baldwin, III.,, and F. Sanfilippo. 1994. The effect of soluble complement receptor type 1 on hyperacute rejection of porcine xenografts. Transplantation 57:363370.
122. Quigg, R. J.,, C. He,, A. Lim,, D. Berthiaume,, J. J. Alexander,, D. Kraus,, and V. M. Holers. 1998. Transgenic mice overexpressing the complement inhibitor crry as a soluble protein are protected from antibody-induced glomerular injury. J. Exp. Med. 188:13211331.
123. Rajasinghe, H. A.,, V. M. Reddy,, W. W. Hancock,, M. H. Sayegh,, and F. L. Hanley. 1996. Key role of the alternate complement pathway in hyperacute rejection of rat hearts transplanted into fetal sheep. Transplantation 62:407411.
124. Rinder, C. S.,, H. M. Rinder,, K. Johnson,, M. Smith,, D. L. Lee,, J. Tracey,, G. Polack,, P. Higgins,, C. G. Yeh,, and B. R. Smith. 1999. Role of C3 cleavage in monocyte activation during extracorporeal circulation. Circulation 100:553558.
125. Rollins, S. A.,, J. C. K. Fitch,, S. Shernan,, C. S. Rinder,, H. M. Rinder,, B. R. Smith,, C. D. Collard,, G. L. Stahl,, B. L. Alford,, L. Li,, and L. A. Matis. 1998. Anti-C5 single chain antibody therapy blocks complement and leukocyte activation and reduces myocardial tissue damage in CPB patients. Mol. Immunol. 35:397.
126. Rollins, S. A.,, L. A. Matis,, J. P. Springhorn,, E. Setter,, and D. W. Wolff. 1995. Monoclonal antibodies directed against human C5 and C8 block complement-mediated damage of xenogeneic cells and organs. Transplantation 60:12841292.
127. Rosengard, A. M.,, N. R. B. Cary,, G. A. Langford,, A. W. Tucker,, J. Wallwork,, and D. J. G. White. 1995. Tissue expression of human complement inhibitor, decay-accelerating factor, in transgenic pigs: a potential approach for preventing xenograft rejection. Transplantation 59:13251333.
128. Rosse, W. F.,, and R. E. Ware. 1995. The molecular basis of paroxysmal nocturnal hemoglobinuria. Blood 86:32773286.
129. Rother, K.,, G. O. Till,, and G. M. Hansch (ed.). 1998. The Complement System. Springer, Berlin, Germany.
130. Saadi, S.,, R. A. Holzknecht,, C. Patte,, D. M. Stern,, and J. L. Platt. 1995. Complement-mediated regulation of tissue factor activity in endothelium. J. Exp. Med. 182:18071814.
131. Saadi, S.,, and J. L. Platt,. 1998. Endothelial cell responses to complement activation, p. 335353. In J. E. Volanakis, and M. M. Frank (ed.), The Human Complement System in Health and Disease. Marcel Dekker, Inc., New York, N.Y.
132. Saadi, S.,, and J. L. Platt. 1995. Transient perturbation of endothelial integrity induced by natural antibodies and complement. J. Exp. Med. 181:2131.
133. Sahu, A.,, B. K. Kay,, and J. D. Lambris. 1996. Inhibition of human complement by a C3-binding peptide isolated from a phage-displayed random peptide library. J. Immunol. 157:884891.
134. Salerno, C. T.,, A. P. Dalmasso,, T. J. Kroshus,, C. A. Svendsen,, D. M. Kulick,, S. J. Park,, S. J. Shumway,, M. Guzman,, C. G. Yeh,, P. J. Higgins,, A. A. Kreasy,, and R. M. Bolman. 1997. A recombinant soluble chimeric complement inhibitor CAB-2.0 prolongs xenograft survival in a heterotopic model of pig-to-primate cardiac transplantation. Surg. Forum 48:265267.
135. Sandrin, M. S.,, H. A. Vaughan,, P. L. Dabkowski,, and I. F. C. McKenzie. 1993. Anti-pig IgM antibodies in human serum react predominantly with Gal(αl-3)Gal epitopes. Proc. Natl. Acad. Sci. USA 90:1139111395.
136. Schaapherder, A. F. M.,, H. G. Gooszen,, M. T. J. W. Te Bulte,, and M. R. Daha. 1995. Human complement activation via the alternative pathway on porcine endothelium initiated by IgA antibodies. Transplantation 60:287291.
137. Schmoeckel, M.,, F. N. Bhatti,, A. Zaidi,, E. Cozzi,, P. D. Waterworth,, M. J. Tolan,, G. Pino-Chavez,, M. Goddard,, R. G. Warner,, G. A. Langford,, J. J. Dunning,, J. Wallwork,, and D. J. G. White. 1998. Orthotopic heart transplantation in a transgenic pig-to-primate model. Transplantation 65:15701577.
138. Schmoeckel, M.,, G. Nollert,, M. Shahmohammadi,, J. Muller-Hocker,, V. K. Young,, W. Kasper-Konig,, D. J. White,, C. Hammer,, and B. Reichart. 1997. Transgenic human decay accelerating factor makes normal pigs function as a concordant species. J. Heart Lung Transplant. 16:758764.
139. Schmoeckel, M.,, G. Nollert,, M. Shahmohammadi,, Y. V. K.,, G. Chavez,, W. Kasper-Konig,, D. J. G. White,, J. Muller-Hocker,, R. M. Arendt,, U. Wilbert-Lampen,, C. Hammer,, and B. Reichart. 1996. Prevention of hyperacute rejection by human decay accelerating factor in xenogeneic perfused working hearts. Transplantation 62:729734.
140. Selvan, R. S.,, H. B. Kapadia,, and J. L. Platt. 1998. Complement-induced expression of chemokine genes in endothelium: regulation by IL-1-dependent and -independent mechanisms. J. Immunol. 161:4388395.
141. Sharma, A.,, J. Okabe,, P. Birch,, M. S. B.,, M. J. Martin,, J. L. Platt,, and J. S. Logan. 1996. Reduction in the level of Gal(αl,3)Gal in transgenic mice and pigs by the expression of an α(l,2)fucosyltransferase. Proc. Natl. Acad. Sci. USA 93:71907195.
142. Shinkel, T. A.,, P. J. Cowan,, H. Barlow,, A. Aminian,, M. Romanella,, D. M. Lublin,, M. J. Pearse,, and A. J. d'Apice. 1998. Expression and functional analysis of glycosyl-phosphatidyl inositol-linked CD46 in transgenic mice. Transplantation 66:14011406.
143. Slapak, M.,, N. Digard,, M. Ahmed,, T. Shell,, and F. Thompson. 1990. Renal transplantation across the ABO barrier: a 9-year experience. Transplant. Proc. 22:14251428.
144. Soares, M. P.,, Y. Lin,, J. Anrather,, E. Csizmadia,, K. Takigami,, K. Sato,, S. T. Grey,, R. B. Colvin,, A. M. Choi,, K. D. Poss,, and F. H. Bach. 1998. Expression of heme oxygenase-1 can determine cardiac xenograft survival. Nature Med. 4:10731077.
145. Somerville, C. A.,, A. G. Kyriazis,, A. McKenzie,, J. Allison,, M. J. Pearse,, and A. J. F. D'Apice. 1994. Functional expression of human CD59 in transgenic mice. Transplantation 58:14301435.
146. Stahl, G. L.,, W. R. Reenstra,, and G. Frendl. 1995. Complement-mediated loss of endothelium-dependent relaxation of porcine coronary arteries. Role of the terminal membrane attack complex. Circ. Res. 76:575583.
147. Stevens, R. B.,, Y. L. Wang,, H. Kaji,, J. Lloveras,, A. Dalmasso,, F. H. Bach,, P. Rubinstein,, D. E. R. Sutherland,, and J. L. Platt 1993. Administration of nonanticoagulant heparin inhibits the loss of glycosaminoglycans from xenogeneic cardiac grafts and prolongs graft survival. Transplant. Proc. 25:382.
148. Stoiber, H.,, A. Clivio,, and M. Dierich. 1997. Role of complement in HIV infection. Ann. Rev. Immunol. 15:649674.
149. Suhr, B. D.,, M. Guzman-Paz,, E. P. Apasova,, A. J. Matas,, and A. P. Dalmasso. Induction of accommodation in the hamster-to-rat model requires inhibition of the membrane attack complex of complement. Transplant. Proc., in press.
150. Suttorp, N.,, W. Seeger,, S. Zinsky,, and S. Bhakdi. 1987. Complement complex C5b-8 induced PGI2 formation in cultured endothelial cells. Am. J. Physiol. 253:C13C21.
151. Taniguchi, S.,, T. Kobayashi,, F. A. Neethling,, Y. Ye,, M. Niekrasz,, D. J. White,, and D. K. Cooper. 1996. Cobra venom factor stimulates anti-alpha-galactose antibody production in baboons. Implications for pig-to-human xenotransplantation. Transplantation 62:678681.
152. Tearle, R. G.,, M. J. Tange,, Z. L. Zannettino,, M. Katerelos,, T. A. Shinkel,, B. J. W. van Denderen,, A. J. Lonie,, I. Lyons,, M. B. Nottle,, T. Cox,, C. Becker,, A. M. Peura,, P.L. Wigley,, R. J. Crawford,, A. J. Robins,, M. J. Pearse,, and A. J. F. d'Apice. 1996. The α-l,3-galactosyltransferase knockout mouse. Implications for xenotransplantation. Transplantation 61:1319.
153. Tedesco, F.,, M. Pausa,, E. Nardon,, M. Introna,, A. Mantovani,, and A. Dobrina. 1997. The cytolytically inactive terminal complement complex activates endothelial cells to express adhesion molecules and tissue factor procoagulant activity. J. Exp. Med. 185:16191627.
154. Thorley, B. R.,, J. Milland,, D. Christiansen,, M. B. Lanteri,, B. Mclnnes,, I. Moeller,, P. Rivailler,, B. Horvat,, C. Rabourdin-Combe,, D. Gerlier,, I. F. McKenzie,, and B. E. Loveland. 1997.Transgenic expression of a CD46 (membrane cofactor protein) minigene: studies of xenotransplantation and measles virus infection. Eur. J. Immunol. 27:726734.
155. Tucker, A. W.,, H. S. Davies,, C. A. Carrington,, A. C. Richards,, K. Elsome,, and D. J. G. White. 1996. The fertility and breeding potential of boars expressing a functional regulator of human complement activation. Transplant. Proc. 28:642.
156. van den Berg, C. W.,, and B. P. Morgan. 1994. Complement-inhibiting activities of human CD59 and analogues from rat, sheep and pig are not homologously restricted. J. Immunol. 152:40954101.
157. vandenBerg, C. W.,, J. M. Perez de la Lastra,, D. Llanes,, and B. P. Morgan. 1997. Purification and characterization of the pig analogue of human membrane cofactor protein (CD46/MCP). J. Immunol. 158:17031709.
158. van Denderen, B. J.,, E. Salvaris,, M. Romanella,, A. Aminian,, M. Katerelos,, M. J. Tange,, M. J. Pearse,, and A. J. d'Apice. 1997. Combination of decay-accelerating factor expression and alpha 1,3-galactosyltransferase knockout affords added protection from human complement-mediated injury. Transplantation 64:882888.
159. Vanhove, B.,, R. de Martin,, J. Lipp,, and F. H. Bach. 1994. Human xenoreactive natural antibodies of the IgM isotype activate pig endothelial cells. Xenotransplantation 1:1723.
160. Varani, J.,, I. Ginsburg,, L. Schuger,, D. F. Gibbs,, J. Bromberg,, K. J. Johnson,, U. S. Ryan,, and P. A. Ward. 1989. Endothelial cell killing by neutrophils. Synergistic interaction of oxygen products and proteases. Am. J. Pathol. 135:435438.
161. Vercellotti, G. M.,, J. L. Platt,, F. H. Bach,, and A. P. Dalmasso. 1991. Neutrophil adhesion to xenogeneic endothelium via iC3b. J. Immunol. 146:730734.
162. Vetvicka, V.,, B. P. Thornton,, and G. D. Ross. 1996. Soluble beta-glucan polysaccharide binding to the lectin site of neutrophil or natural killer cell complement receptor type 3 (CD1lb/CD18) generates a primed state of the receptor capable of mediating cytotoxicity of iC3b-opsonized target cells. J. Clin. Invest. 98:5061.
163. Vogel, C. W.,, and H. J. Muller-Eberhard. 1982. The cobra venom factor-dependent C3 convertase of human complement. J. Biol. Chem. 257:82928299.
164. Volanakis, J. E.,, and M. M. Frank (ed.). 1998. The Human Complement System in Health and Disease. Marcel Dekker, Inc., New York, N.Y.
165. Wagner, E.,, and M. M. Frank,. 1998. Development of clinically useful agents to control complement-mediated tissue damage, p. 527546. In J. E. Volanakis, and M. M. Frank (ed.), The Human Complement System in Health and Disease. Marcel Dekker, Inc., New York, N.Y.
166. Weissman, H. F.,, T. Bartow,, M. K. Leppo,, H. C. MarshJr.,, G. R. Carson,, M. F. Concino,, M. P. Boyle,, K. H. Roux,, M. L. Weisfeldt,, and D. T. Fearon. 1990. Soluble human complement receptor type 1: in vivo inhibitor of complement suppressing post-ischemic myocardial inflammation and necrosis. Science 249:146151.
167. Xia, W.,, D. T. Fearon,, F. D. Moore,Jr.,, F. J. Schoen,, F. Ortiz,, and R. L. Kirkman. 1992. Prolongation of guinea pig cardiac xenograft survival in rats by soluble human complement receptor type 1. Transplant. Proc. 24:479480.
168. Yeatman, M.,, C. W. Daggett,, C. L. Lau,, G. W. Byrne,, J. S. Logan,, J. L. Platt,, and R. D. Davis. 1999. Human complement regulatory proteins protect swine lungs from xenogeneic injury. Ann. Thorac. Surg. 67:769775.
169. Zaidi, A.,, F. Bhatti,, M. Schmoeckel,, E. Cozzi,, G. Chavez,, J. Wallwork,, D. White,, and P. Friend. 1998. Kidneys from HDAF transgenic pigs are physiologically compatible with primates. Transplant Proc. 30:24652466.
170. Zaidi, A.,, M. Schmoeckel,, F. Bhatti,, P. Waterworth,, M. Tolan,, E. Cozzi,, G. Chavez,, G. Langford,, S. Thiru,, J. Wallwork,, D. White,, and P. Friend. 1998. Life-supporting pig-to-primate renal xenotransplantation using genetically modified donors. Transplantation 65:15849150.
171. Zhang, H.,, J. Yu,, E. Bajawa,, S. L. Morrison,, and S. Tomlinson. 1999. Targeting of functional antibody-CD59 fusion proteins to a cell surface. J. Clin. Invest. 103:5561.
172. Zhao, J.,, S. A. Rollins,, S. E. Maher,, A. L. Both well,, and P. J. Sims. 1991. Amplified gene expression in CD59-transfected Chinese hamster ovary cells confers protection against the membrane attack complex of human complement. J. Biol. Chem. 266:1341813421
173. Zhow, X. J.,, N. Niesen,, I. Pawlowski,, G. Biesecker,, G. Andres,, J. Brentjens,, and F. Milgrom. 1990. Prolongation of survival of discordant kidney xenografts by C6 deficiency. Transplantation 50:896898.


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Table 1

Proteins of the complement system

Citation: Dalmasso A. 2001. The Complement System as a Hurdle to Xenotransplantation, p 55-83. In Platt J (ed), Xenotransplantation. ASM Press, Washington, DC. doi: 10.1128/9781555818043.ch3
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Table 2

Effects of complement activation products on endothelial cells and vessels of the xenograft and blood cells of the recipient

Citation: Dalmasso A. 2001. The Complement System as a Hurdle to Xenotransplantation, p 55-83. In Platt J (ed), Xenotransplantation. ASM Press, Washington, DC. doi: 10.1128/9781555818043.ch3
Generic image for table
Table 3

Soluble inhibitors of complement activation used in models of xenotransplantation

Citation: Dalmasso A. 2001. The Complement System as a Hurdle to Xenotransplantation, p 55-83. In Platt J (ed), Xenotransplantation. ASM Press, Washington, DC. doi: 10.1128/9781555818043.ch3

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