Induction of carbon monoxide in donor animals prior to organ procurement reduces graft immunogenicity and inhibits chronic allograft dysfunction.
BACKGROUND
Nonspecific inflammatory damages occurring prior to organ transplantation reduce long-term graft survival. Here, we tested the beneficial effects of carbon monoxide (CO) induction by methylene chloride (MC).


METHODS
Fischer-344 (F-344 Rat) or Dark Agouti (DA Rat) donor animals were either treated with MC four hours prior to organ removal or remained untreated. Kidneys were transplanted into Lewis (LEW) recipients. The low responder strain combination (F-344-->LEW) was studied for long-term graft changes. Dendritic cells (DCs) migration and early changes were followed in additional groups of a high responding donor/recipient strain combination (DA-->LEW). Native kidneys of uninephrectomized, age-matched normal animals served as controls.


RESULTS
Following MC application COHb peaked within two hours in donor animals. Renal function and morphology improved significantly in renal allografts of CO induced donor animals and were comparable to native controls long-term (24 wks). Early after transplantation (24 hr) donor-derived DCs, CD4+ T-cells and alloreactive T-cells were significantly reduced following the engraftment of organs from treated donors. In addition, a trend towards a Th1/Th2 shift and a significant intragraft reduction of CD3 mRNA expression was observed.


CONCLUSIONS
Donor treatment for the induction of CO reduced graft immunogenicity and inhibited chronic allograft nephropathy.
Martins
Paulo Ney Aguiar
PN
Division of Transplant Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Reutzel-Selke
Anja
A
Jurisch
Anke
A
Denecke
Christian
C
Attrot
Kirstin
K
Pascher
Andreas
A
Kotsch
Katja
K
Pratschke
Johann
J
Neuhaus
Peter
P
Volk
Hans-Dieter
HD
Tullius
Stefan G
SG
D000818:Animals; D017252:CD3 Complex / Q000235:genetics; D002248:Carbon Monoxide / Q000378:metabolism*; D002263:Carboxyhemoglobin / Q000378:metabolism; D016207:Cytokines / Q000235:genetics; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D007249:Inflammation; D007677:Kidney Function Tests; D016030:Kidney Transplantation / Q000276:immunology / Q000502:physiology*; D008752:Methylene Chloride / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D011916:Rats, Inbred F344; D011917:Rats, Inbred Lew; D020133:Reverse Transcriptase Polymerase Chain Reaction; D020858:Tissue and Organ Harvesting / Q000379:methods*; D014184:Transplantation, Homologous / Q000276:immunology / Q000502:physiology*
D017252:CD3 Complex; D016207:Cytokines; D012333:RNA, Messenger; D008752:Methylene Chloride; D002248:Carbon Monoxide; D002263:Carboxyhemoglobin