Document Detail

Transgenic swine lungs expressing human CD59 are protected from injury in a pig-to-human model of xenotransplantation.
MedLine Citation:
PMID:  10733757     Owner:  NLM     Status:  MEDLINE    
BACKGROUND: Pulmonary xenotransplantation is currently limited by hyperacute rejection mediated in part by xenoreactive natural antibody and complement. Transgenic swine organs that express the human complement regulatory protein CD59 have demonstrated improved survival in models of pig-to-primate xenotransplantation. OBJECTIVE: The purpose of this study was to evaluate transgenic swine lungs that express the human complement regulatory protein CD59 in a model of pig-to-human xenotransplantation. METHODS: Transgenic swine lungs (n = 5, experimental group) and outbred swine lungs (n = 6, control group) were perfused with fresh, whole human blood through a centrifugal pump on an ex vivo circuit. Functional data were collected throughout perfusion. Immunoglobulin and complement studies were performed on perfusate samples, and both histologic and immunofluorescent analyses were performed on tissue sections. RESULTS: Mean lung survival for the experimental group was increased when compared with controls, 240 +/- 0 minutes versus 35.3 +/- 14.5 minutes, respectively, with a P value of less than.01. A decreased rise in pulmonary vascular resistance at 15 minutes was observed in the experimental group (343 +/- 87 mm Hg. L(-1). min(-1), in contrast to the control group (1579 +/- 722 mm Hg. L(-1). min(-1); P <.01). Pulmonary compliance at 15 minutes was improved for the experimental group versus control group (9.31 +/- 1.41 mL. cm(-2) H(2)O and 4.11 +/- 2.84 mL. cm(-2) H(2)O, respectively; P <.01). SC5b-9 generation in the plasma perfusate was delayed for the experimental group versus the control group. Immunofluorescent examination of tissue sections demonstrated equivalent deposition of immunoglobulin G, immunoglobulin M, C1q, and C3 in both groups, with reduced deposition of C9 in the experimental group. CONCLUSIONS: Transgenic swine pulmonary xenografts that express the human complement regulatory protein CD59 demonstrated improved function and survival in an ex vivo model of pig-to-human xenotransplantation.
D M Kulick; C T Salerno; A P Dalmasso; S J Park; M G Paz; W L Fodor; R M Bolman
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Publication Detail:
Type:  In Vitro; Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.    
Journal Detail:
Title:  The Journal of thoracic and cardiovascular surgery     Volume:  119     ISSN:  0022-5223     ISO Abbreviation:  J. Thorac. Cardiovasc. Surg.     Publication Date:  2000 Apr 
Date Detail:
Created Date:  2000-05-18     Completed Date:  2000-05-18     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0376343     Medline TA:  J Thorac Cardiovasc Surg     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  690-9     Citation Subset:  AIM; IM    
Department of Surgery, University of Minnesota, Minneapolis 55455, USA.
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MeSH Terms
Antigens, CD59 / analysis*
Complement C3a / analysis
Complement Hemolytic Activity Assay
Fluorescent Antibody Technique
Graft Survival / immunology*
Immunoglobulin G / analysis
Immunoglobulin M / analysis
Lung / immunology,  pathology
Lung Compliance
Lung Transplantation / immunology*
Pulmonary Circulation
Transplantation, Heterologous / immunology*
Vascular Resistance
Reg. No./Substance:
0/Antigens, CD59; 0/Immunoglobulin G; 0/Immunoglobulin M; 80295-42-7/Complement C3a

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