Document Detail


Induction of carbon monoxide in donor animals prior to organ procurement reduces graft immunogenicity and inhibits chronic allograft dysfunction.
MedLine Citation:
PMID:  17038910     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Paulo Ney Aguiar Martins; Anja Reutzel-Selke; Anke Jurisch; Christian Denecke; Kirstin Attrot; Andreas Pascher; Katja Kotsch; Johann Pratschke; Peter Neuhaus; Hans-Dieter Volk; Stefan G Tullius
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Transplantation     Volume:  82     ISSN:  0041-1337     ISO Abbreviation:  Transplantation     Publication Date:  2006 Oct 
Date Detail:
Created Date:  2006-10-13     Completed Date:  2006-11-27     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0132144     Medline TA:  Transplantation     Country:  United States    
Other Details:
Languages:  eng     Pagination:  938-44     Citation Subset:  IM    
Affiliation:
Division of Transplant Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Antigens, CD3 / genetics
Carbon Monoxide / metabolism*
Carboxyhemoglobin / metabolism
Cytokines / genetics
Dendritic Cells / drug effects,  immunology
Enzyme-Linked Immunosorbent Assay
Flow Cytometry
Inflammation
Kidney Function Tests
Kidney Transplantation / immunology,  physiology*
Methylene Chloride / pharmacology*
RNA, Messenger / genetics
Rats
Rats, Inbred F344
Rats, Inbred Lew
Reverse Transcriptase Polymerase Chain Reaction
Tissue and Organ Harvesting / methods*
Transplantation, Homologous / immunology,  physiology*
Chemical
Reg. No./Substance:
0/Antigens, CD3; 0/Cytokines; 0/RNA, Messenger; 630-08-0/Carbon Monoxide; 75-09-2/Methylene Chloride; 9061-29-4/Carboxyhemoglobin

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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