| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
American Journal of Pathology, Vol 140, 1157-1166, Copyright © 1992 by American Society for Investigative Pathology
REGULAR ARTICLES |
AP Dalmasso, GM Vercellotti, RJ Fischel, RM Bolman, FH Bach and JL Platt
Veterans Affairs Medical Center, Minneapolis, MN 55417.
The authors investigated the importance of natural antibody and complement in the pathogenesis of hyperacute xenograft rejection using in vivo and in vitro pig to primate models. Studies were carried out in rhesus monkeys transplanted with a pig heart or kidney in which hyperacute rejection was observed within a few hours. The rejected organs showed deposits of IgM, C3, C4, C5, and C9 neoantigen along small blood vessels, but few deposits of factors B and P. Removal of anti-endothelial cell "natural" antibodies by plasmapheresis, immunoabsorption, and immunosuppression techniques resulted in marked prolongation of the survival of a subsequently transplanted heart, even when complement levels were within the normal range. Thus, complement, in the absence of natural antibodies, did not initiate hyperacute rejection in this species combination. The requirements for complement activation in human serum to cause cytotoxicity of porcine endothelial cells were then evaluated. Cytotoxicity was abrogated by depleting human serum of IgM, C2, or C5, but not of factor B. Restoration of the effect of serum on endothelial cells was achieved by reconstitution of the respective depleted sera with purified IgM or with the corresponding complement proteins, indicating that IgM and the classical, but not the alternative, pathway of complement, were involved. Identical conclusions were drawn from experiments to ascertain the requirements for complement activation in human serum to mediate binding of iC3b to porcine endothelial cells. The authors conclude that in a pig to primate xenograft complement does not directly initiate injury to the graft but rather requires activation by bound xenoreactive natural antibodies; IgM antibodies directed against endothelial cells activate the classical complement pathway, which then contributes to endothelial cell activation and subsequent events characteristic of hyperacute rejection.
This article has been cited by other articles:
 |
|
 |
|
  M. Saethre, M. K. J. Schneider, J. D. Lambris, P. Magotti, G. Haraldsen, J. D. Seebach, and T. E. Mollnes Cytokine Secretion Depends on Gal{alpha}(1,3)Gal Expression in a Pig-to-Human Whole Blood Model J. Immunol., May 1, 2008; 180(9): 6346 - 6353. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. M. Black, J. F. Grehan, A. L. Rivard, B. A. Benson, A. E. Wahner, A. E. Koch, B. K. Levay-Young, and A. P. Dalmasso Porcine Endothelial Cells and Iliac Arteries Transduced with AdenoIL-4 Are Intrinsically Protected, through Akt Activation, against Immediate Injury Caused by Human Complement J. Immunol., November 15, 2006; 177(10): 7355 - 7363. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. F. Grehan, B. K. Levay-Young, J. L. Fogelson, V. Francois-Bongarcon, B. A. Benson, and A. P. Dalmasso IL-4 and IL-13 Induce Protection of Porcine Endothelial Cells from Killing by Human Complement and from Apoptosis through Activation of a Phosphatidylinositide 3-Kinase/Akt Pathway J. Immunol., August 1, 2005; 175(3): 1903 - 1910. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Al-Mohanna, S. Saleh, R. S. Parhar, K. Khabar, and K. Collison Human neutrophil gene expression profiling following xenogeneic encounter with porcine aortic endothelial cells: the occult role of neutrophils in xenograft rejection revealed J. Leukoc. Biol., July 1, 2005; 78(1): 51 - 61. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. M. Dufour, M. Hamilton, R. V. Rajotte, and G. S. Korbutt Neonatal Porcine Sertoli Cells Inhibit Human Natural Antibody-Mediated Lysis Biol Reprod, May 1, 2005; 72(5): 1224 - 1231. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Sheikh, R. Parhar, and F. Al-Mohanna Rapid static adhesion of human naive neutrophil to naive xenoendothelium under physiologic flow is independent of Gal{alpha}1,3-gal structures J. Leukoc. Biol., June 1, 2002; 71(6): 932 - 940. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Costa, D. F. Barber, and W. L. Fodor Human NK Cell-Mediated Cytotoxicity Triggered by CD86 and Gal{alpha}1,3-Gal Is Inhibited in Genetically Modified Porcine Cells J. Immunol., April 15, 2002; 168(8): 3808 - 3816. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Z. E. Holzknecht, S. Coombes, B. A. Blocher, T. B. Plummer, M. Bustos, C. L. Lau, R. D. Davis, and J. L. Platt Immune Complex Formation after Xenotransplantation : Evidence of Type III as well as Type II Immune Reactions Provide Clues to Pathophysiology Am. J. Pathol., February 1, 2001; 158(2): 627 - 637. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. M. Kulick, C. T. Salerno, A. P. Dalmasso, S. J. Park, M. G. Paz, W. L. Fodor, and R. M. Bolman III TRANSGENIC SWINE LUNGS EXPRESSING HUMAN CD59 ARE PROTECTED FROM INJURY IN A PIG-TO-HUMAN MODEL OF XENOTRANSPLANTATION J. Thorac. Cardiovasc. Surg., April 1, 2000; 119(4): 690 - 699. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. P. Dalmasso, B. A. Benson, J. S. Johnson, C. Lancto, and M. S. Abrahamsen Resistance Against the Membrane Attack Complex of Complement Induced in Porcine Endothelial Cells with a Gal{alpha}(1-3)Gal Binding Lectin: Up-Regulation of CD59 Expression J. Immunol., April 1, 2000; 164(7): 3764 - 3773. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Grimm, P. Mages, G. Lindemann, M. Potthoff, U. Bohnet, S. Korom, and L. Ermert EVIDENCE AGAINST A PIVOTAL ROLE OF PREFORMED ANTIBODIES IN DELAYED REJECTION OF A GUINEA PIG-TO-RAT HEART XENOGRAFT J. Thorac. Cardiovasc. Surg., March 1, 2000; 119(3): 477 - 487. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Kearns-Jonker, J. Swensson, C. Ghiuzeli, W. Chu, Y. Osame, V. Starnes, and D. V. Cramer The Human Antibody Response to Porcine Xenoantigens Is Encoded by IGHV3-11 and IGHV3-74 IgVH Germline Progenitors J. Immunol., October 15, 1999; 163(8): 4399 - 4412. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. COSTA, L. ZHAO, W. V. BURTON, K. R. BONDIOLI, B. L. WILLIAMS, T. A. HOAGLAND, P. A. DITULLIO, K. M. EBERT, and W. L. FODOR Expression of the human {alpha}1,2-fucosyltransferase in transgenic pigs modifies the cell surface carbohydrate phenotype and confers resistance to human serum-mediated cytolysis FASEB J, October 1, 1999; 13(13): 1762 - 1773. [Abstract] [Full Text]
|
|
|
|
 |
|
 S. C. ROBSON, J. S. AM ESCH II, and F. H. BACH Factors in Xenograft Rejection Ann. N.Y. Acad. Sci., June 18, 1999; 875(1): 261 - 276. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Brenner, M. Hinz, H. Huber, M. Schmoeckel, H. Reichenspurner, B. Meiser, C. Hammer, and B. Reichart The influence of antibody and complement removal with a Ig-Therasorb column in a xenogeneic working heart model Eur. J. Cardiothorac. Surg., May 1, 1999; 15(5): 672 - 679. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. L. PLATT and S. S. LIN The Future Promises of Xenotransplantation Ann. N.Y. Acad. Sci., December 30, 1998; 862(1): 5 - 18. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. A. Robinson, L. Tu, D. A. Steeber, O. Preis, J. L. Platt, and T. F. Tedder The Role of Adhesion Molecules in Human Leukocyte Attachment to Porcine Vascular Endothelium: Implications for Xenotransplantation J. Immunol., December 15, 1998; 161(12): 6931 - 6938. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Sepp, P. Skacel, R. Lindstedt, and R. I. Lechler Expression of alpha -1,3-Galactose and Other Type 2 Oligosaccharide Structures in a Porcine Endothelial Cell Line Transfected with Human alpha -1,2-Fucosyltransferase cDNA J. Biol. Chem., September 12, 1997; 272(37): 23104 - 23110. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Macchiarini, G.-M. Mazmanian, R. Oriol, V. de Montpreville, E. Dulmet, S. Fattal, J.-M. Libert, S. Doubine, D. Nochy, R. Rieben, et al. EX VIVO LUNG MODEL OF PIG-TO-HUMAN HYPERACUTE XENOGRAFT REJECTION J. Thorac. Cardiovasc. Surg., September 1, 1997; 114(3): 315 - 325. [Abstract] [Full Text]
|
|
|
|
|
|
H. Ogawa, H. Muramatsu, T. Kobayashi, K. Morozumi, I. Yokoyama, N. Kurosawa, A. Nakao, and T. Muramatsu 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., June 16, 2000; 275(25): 19368 - 19374. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
