Leukocyte infiltration and inflammatory antigen expression in cadaveric and living-donor livers before transplant.
BACKGROUND
There is evidence to indicate that organs obtained from cadaveric donors may be injured as a result of inflammatory events occurring at around the time of brain death. The aim of this study was to investigate whether there are differences in the expression of proinflammatory molecules between cadaveric and living-donor livers before transplant and to determine whether there is any association with donor factors and posttransplant graft function.


METHODS
A comparison of biopsies obtained before implantation from cadaveric (n=22) and living-related donor (LRD) (n=10) livers was performed. Cryostat tissue sections were stained with antibodies to leukocyte subpopulations, adhesion molecules, and human leukocyte antigen class II antigens.


RESULTS
Significantly higher levels of CD3+ lymphocytes (1.5%+/-0.8% vs. 0.5%+/-0.3%; P=0.00004), CD68+ monocytes and macrophages (4.0%+/-1.2% vs. 2.7%+/-0.6%; P=0.0003), and Fas-ligand staining (4.2%+/-2.6% vs. 1.5%+/-1.1%; P=0.0003) were detected in cadaveric livers compared with LRD livers before transplantation. Furthermore, higher levels of intercellular adhesion molecule-1 expression were detected in cadaveric donor livers and found to be associated with longer periods of ventilation (P=0.01), infection in the donor (P=0.013), and administration of dopamine (P=0.03). Although there were no differences in neutrophil infiltration between cadaveric and LRD livers, significantly higher levels were found in cadaveric donors with infection (P=0.01).


CONCLUSIONS
This study demonstrates that inflammatory changes occur in cadaveric donor livers and are associated with events occurring during the period of intensive care. These proinflammatory changes did not seem to affect the short-term clinical outcome of cadaveric liver allografts but may contribute to alloimmune responses and impairment of graft function in the long term.
Jassem
Wayel
W
Liver Transplant Unit, Institute of Liver Studies, King's College Hospital, Denmark Hill, London, United Kingdom.
Koo
Dicken D H
DD
Cerundolo
Lucia
L
Rela
Mohamed
M
Heaton
Nigel D
ND
Fuggle
Susan V
SV
D015703:Antigens, CD / Q000032:analysis; D001706:Biopsy; D001926:Brain Death / Q000276:immunology; D002102:Cadaver; D002634:Chemotaxis, Leukocyte / Q000502:physiology*; D006681:HLA-D Antigens / Q000032:analysis; D006801:Humans; D007150:Immunohistochemistry; D007249:Inflammation / Q000276:immunology*; D008099:Liver / Q000166:cytology / Q000473:pathology; D008111:Liver Function Tests; D016031:Liver Transplantation / Q000502:physiology*; D019520:Living Donors; D017260:Receptor-CD3 Complex, Antigen, T-Cell / Q000032:analysis
D015703:Antigens, CD; D006681:HLA-D Antigens; D017260:Receptor-CD3 Complex, Antigen, T-Cell