Lecithinized superoxide dismutase reduces cold ischemia-induced chronic allograft dysfunction.
BACKGROUND
Chronic renal allograft failure (CAF) is influenced by both allo-dependent and independent factors and is a major cause of graft loss in clinical renal transplantation. We evaluated a novel membrane-bound free radical scavenger, lecithinized superoxide dismutase (lec-SOD), to determine its potential in limiting the harmful effects of ischemia/reperfusion injury on CAF.


METHODS
Fisher rat kidneys were stored for either 1 hour or 18 hours in cold Marshall's preservation solution either with or without lec-SOD and transplanted into Lewis recipients.


RESULTS
Within 3 days of transplantation, an early inflammatory response involving granulocytes and macrophages was detected in renal allografts exposed to 18 hours cold ischemia that was significantly reduced by preservation with lec-SOD. By 24 weeks post-transplantation, elevated proteinuria and detection of apoptotic cells was observed in kidneys exposed to 18 hours of cold ischemia, that was attenuated by preservation with lec-SOD (P < 0.05). However, up-regulated expression of intracellular adhesion molecule-1 (ICAM-1) and major histocompatibility complex (MHC) Class II together with a T lymphocyte infiltration were observed at 24 weeks that was not prevented by preservation with lec-SOD.


CONCLUSIONS
These results demonstrate that ischemia/reperfusion injury, apoptotic cell death and allo-immune responses may be exacerbated by cold ischemia and accelerate the development of CAF. Preservation with lec-SOD may protect against the early damage induced by cold ischemia and reperfusion injury.
Nakagawa
Ken
K
Nuffield Department of Surgery, University of Oxford, John Radcliffe Hospital, Headington, Oxford, OX3 9DU, United Kingdom.
Koo
Dicken D H
DD
Davies
David R
DR
Gray
Derek W R
DW
McLaren
Andrew J
AJ
Welsh
Kenneth I
KI
Morris
Peter J
PJ
Fuggle
Susan V
SV
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D015925:Cryopreservation; D016166:Free Radical Scavengers / Q000494:pharmacology*; D015395:Histocompatibility Antigens Class I / Q000378:metabolism; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D007511:Ischemia / Q000473:pathology / Q000503:physiopathology*; D007668:Kidney / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology*; D016030:Kidney Transplantation; D007962:Leukocytes / Q000473:pathology; D008297:Male; D010713:Phosphatidylcholines / Q000494:pharmacology*; D051381:Rats; D011916:Rats, Inbred F344; D011917:Rats, Inbred Lew; D011994:Recombinant Proteins / Q000494:pharmacology; D012079:Renal Circulation; D015427:Reperfusion Injury / Q000473:pathology / Q000503:physiopathology; D013482:Superoxide Dismutase / Q000494:pharmacology*
D016166:Free Radical Scavengers; D015395:Histocompatibility Antigens Class I; D010713:Phosphatidylcholines; D011994:Recombinant Proteins; D018799:Intercellular Adhesion Molecule-1; D013482:Superoxide Dismutase; C434045:lecithinized superoxide dismutase