Induction of carbon monoxide in donor animals prior to organ procurement reduces graft immunogenicity and inhibits chronic allograft dysfunction.

Abstract:

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. CONCLUSION:Donor treatment for the induction of CO reduced graft immunogenicity and inhibited chronic allograft nephropathy.

journal_name

Transplantation

journal_title

Transplantation

authors

Martins PN,Reutzel-Selke A,Jurisch A,Denecke C,Attrot K,Pascher A,Kotsch K,Pratschke J,Neuhaus P,Volk HD,Tullius SG

doi

10.1097/01.tp.0000232716.91887.c5

subject

Has Abstract

pub_date

2006-10-15 00:00:00

pages

938-44

issue

7

eissn

0041-1337

issn

1534-6080

pii

00007890-200610150-00014

journal_volume

82

pub_type

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