HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Personal Folders Download to citation manager Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Macchiarini, P Articles by Dartevelle, P Search for Related Content PubMed PubMed Citation Articles by Macchiarini, P Articles by Dartevelle, P

The Journal of Thoracic and Cardiovascular Surgery, Vol 116, 831-843, Copyright © 1998 by The American Association for Thoracic Surgery and The Western Thoracic Surgical Association

ARTICLES

Evidence of human non-alpha-galactosyl antibodies involved in the hyperacute rejection of pig lungs and their removal by pig organ perfusion

P Macchiarini, R Oriol, A Azimzadeh, V de Montpreville, R Rieben, N Bovin, M Mazmanian and P Dartevelle
Department of Thoracic and Vascular Surgery, Hopital Marie-Lannelongue, Le Plessis Robinson, Paris-Sud University, France.

BACKGROUND: Human natural xenoantibodies represent a major hurdle to the clinical application of pig lungs in transplantation by initiating hyperacute rejection within minutes to hours. OBJECTIVE: The object was to compare pig organ perfusion and specific depletion of anti-alpha- galactosyl xenoantibodies for prevention of hyperacute rejection in the pig to human lung combination. METHODS: Large White pig (20-25 kg) left lungs were removed and continuously ventilated and reperfused ex vivo either with (1) whole human blood previously perfused in situ through pig right lung (group I), liver (group II), or spleen (group III) or with (2) human plasma in vitro immunoabsorbed on columns containing alpha-galactosyl disaccharide (Gal-alpha-(1-3)Gal-beta-(CH2)3NH2; B disaccharide) (group IV). Each study group included 6 animals. RESULTS: The in situ and in vitro preperfusions depleted anti-alpha-galactosyl xenoantibodies and all in situ perfused pig organs showed histologic signs of hyperacute rejection. After the ex vivo reperfusion, group I xenografts had a significantly (P < .001) longer functional and histologic survival than did xenografts in groups II, III, and IV. Human blood reperfusing group I xenografts had a significantly (P < 0.05) lower (1) decline of clotting factors and total circulating immunoglobulins, (2) total and membrane attack complex (C5b,6,7,8,9) complement activation, and (3) hemolysis. By Western blot analysis, the in situ lung preperfusion removed antibodies against non-alpha- galactosyl proteins of low molecular weight that were not eliminated by the alpha-galactosyl column. CONCLUSIONS: Results demonstrate that specific depletion of anti-alpha-galactosyl antibodies alone incompletely protects pig lungs from hyperacute rejection. It is speculated that the more complete prevention of this rejection afforded by pig lung preperfusion relates to the removal of other, non-alpha- galactosyl antibodies.

This article has been cited by other articles:

				S. Pfeiffer, G. L. Zorn III, S. Kelishadi, R. Oriol, P. Wolf, R. N. Pierson III, and A. M. Azimzadeh Role of anti-Gal{alpha}1,3Gal and anti-platelet antibodies in hyperacute rejection of pig lung by human blood Ann. Thorac. Surg., November 1, 2001; 72(5): 1681 - 1690. [Abstract] [Full Text] [PDF]

				C. L. Lau, W. C. Daggett, M. F. Yeatman, P. Chai, S. S. Lin, A. J. Lodge, E. P. Chen, L. E. Diamond, G. W. Byrne, J. S. Logan, et al. The role of antibodies in dysfunction of pig-to-baboon pulmonary transplants J. Thorac. Cardiovasc. Surg., July 1, 2000; 120(1): 29 - 38. [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]

				P. Macchiarini, R. Oriol, A. Azimzadeh, V. de Montpreville, P. Wolf, and P. Dartevelle CHARACTERIZATION OF A PIG-TO-GOAT ORTHOTOPIC LUNG XENOTRANSPLANTATIONMODEL TO STUDY BEYOND HYPERACUTE REJECTION J. Thorac. Cardiovasc. Surg., November 1, 1999; 118(5): 805 - 814. [Abstract] [Full Text] [PDF]