Accommodation after lung xenografting from hamster to rat.
BACKGROUND
Long-term xenograft survival can be achieved in hamster hearts transplanted into rats treated with cobra venom factor (CVF) and cyclosporine A (CsA). This phenomenon of "accommodation" is associated with expression of protective genes such as bcl-2, bcl-X(L), and heme-oxygenase-1. We examined whether accommodation could be induced in hamster-to-rat lung xenografts and whether the pattern of protective genes is similar to cardiac xenografts.


METHODS
We used hamster-to-rat cardiac and lung xenotransplantation models. Cardiac xenotransplants were treated with CVF+CsA and compared with untreated controls. Lung xenotransplants were treated with either CVF+CsA or FK506 and cyclophosphamide (Cp) and compared with untreated controls. All recipients were killed by 21 days after transplantation. We examined graft survival and protein expression of protective genes, and we performed histologic and immunohistologic analyses.


RESULTS
Rejection occurred rapidly in untreated rats. CVF+CsA or FK506+Cp treatment significantly influenced graft survival. Eight of 12 CVF+CsA-treated heart transplants survived 21 days. Seven of 16 CVF+CsA-treated lung grafts and five of 12 FK506+Cp-treated lung xenografts survived 21 days. We observed significant protein expression of bcl-2, bcl-X(L), and heme-oxygenase-1 in cardiac xenografts treated with CVF+CsA at 2, 14, and 21 days after transplantation, compared with normal hamster hearts. We also observed significant expression of these proteins in lung xenografts treated with either CVF+CsA or FK506+Cp at 21 days after transplantation, compared with normal lungs.


CONCLUSIONS
Accommodation may be a general phenomenon for all organs, mediated through protective genes. Induction of accommodation does not require disruption of the complement system.
Tabata
Toshiharu
T
Thoracic Surgery Research Laboratory, Toronto General Hospital Research Institute, University Health Network, University of Toronto, Toronto, Ontario, Canada.
de Perrot
Marc
M
Keshavjee
Shaf
S
Liu
Mingyao
M
Downey
Gregory P
GP
Waddell
Thomas K
TK
D000222:Adaptation, Physiological / Q000235:genetics; D000818:Animals; D015941:Complement Hemolytic Activity Assay; D003169:Complement Inactivator Proteins / Q000494:pharmacology; D006224:Cricetinae; D019610:Cytoprotection / Q000235:genetics; D015870:Gene Expression; D006085:Graft Survival / Q000187:drug effects; D016027:Heart Transplantation; D006419:Heme Oxygenase (Decyclizing) / Q000378:metabolism; D051547:Heme Oxygenase-1; D007166:Immunosuppressive Agents / Q000494:pharmacology; D008168:Lung / Q000378:metabolism / Q000473:pathology; D016040:Lung Transplantation; D008647:Mesocricetus; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051381:Rats; D011917:Rats, Inbred Lew; D014183:Transplantation, Heterologous; D051020:bcl-X Protein
C494813:Bcl2l1 protein, rat; D003169:Complement Inactivator Proteins; D007166:Immunosuppressive Agents; D019253:Proto-Oncogene Proteins c-bcl-2; D051020:bcl-X Protein; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1