Endothelial cell chimerism after renal transplantation in a rat model.
BACKGROUND
Endothelial chimerism, that is, the replacement of damaged donor endothelium by recipient precursors, has been proposed to reduce the allogeneic stimulus and graft rejection. However, both its mechanism and consequence are poorly understood. In this study, we set up a rat model of renal transplantation to investigate the phenomenon of endothelial chimerism and the relationship among the factors involved in its induction, such as preischemic injury, severity of graft rejections, and the role of cyclosporine A toxicity.


METHODS
Female Lewis rats received renal transplants from male Brown Norway kidneys. Groups were divided according to ischemia or nonischemia of the donor kidney and cyclosporine treatment or nonimmunosuppression. To investigate the endothelial chimerism, an in situ hybridization by an X-chromosome-specific DNA probe was performed. The severity of allograft rejection was scored according to the Banff '97 classification.


RESULTS
In grafts without preischemic injury or without cyclosporine A treatment, a low degree of endothelial chimerism was detected, although severe vascular rejection and tissue necrosis developed. More chimerism was found in recipients receiving an ischemic kidney followed by immunosuppressive treatment, although less severe rejection developed. In recipients receiving an ischemic kidney without cyclosporine A treatment, the highest degree of endothelial chimerism occurred.


CONCLUSIONS
Endothelial chimerism demonstrated in rats after renal transplantation may be caused by endothelial damage induced by vascular rejection or ischemia. Ischemia had the strongest association with the induction of chimerism, which may function as a synergistic promoter. A low-dose cyclosporine A treatment was shown to inhibit endothelial replacement.
Xu
Wei
W
Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands.
Baelde
Hans J
HJ
Lagaaij
Emma L
EL
De Heer
Emile
E
Paul
Leendert C
LC
Bruijn
Jan A
JA
D000818:Animals; D016572:Cyclosporine / Q000008:administration & dosage / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects / Q000473:pathology*; D005260:Female; D006084:Graft Rejection; D007165:Immunosuppression Therapy; D007511:Ischemia / Q000503:physiopathology; D007668:Kidney / Q000473:pathology; D016030:Kidney Transplantation; D008297:Male; D009336:Necrosis; D051381:Rats; D011914:Rats, Inbred BN; D011917:Rats, Inbred Lew; D012079:Renal Circulation; D018183:Transplantation Chimera
D016572:Cyclosporine