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- Title
Endothelial cell protection against ischemia/reperfusion injury by lecithinized superoxide dismutase.
- Authors
Koo, Dicken D.H.; Welsh, Kenneth I.; West, Nick E.J.; Channon, Keith M.; Penington, Anthony J.; Roake, Justin A.; Morris, Peter J.; Fuggle, Susan V.; Koo, D D; Welsh, K I; West, N E; Channon, K M; Penington, A J; Roake, J A; Morris, P J; Fuggle, S V
- Abstract
<bold>Background: </bold>Organs used for transplantation may experience long periods of cold ischemic preservation and consequently oxygen free radical-mediated damage following reperfusion. Lecithinized superoxide dismutase (lec-SOD) is a novel free radical scavenger that has been shown to bind with high affinity to cell membranes. The aim of this study was to determine whether lec-SOD bound to endothelial cells under organ preservation conditions to mediate direct antioxidant activity at the endothelial cell surface and thus offer protection against the harmful effects of ischemia/reperfusion injury.<bold>Methods: </bold>An in vitro study was performed on large vessel endothelial cells (HUVEC) and a human microvascular endothelial cell line HMEC-1, to investigate the potential therapeutic benefits of incorporating lec-SOD into organ preservation solution. A cold hypoxia/reoxygenation system was developed to examine lec-SOD binding affinity to endothelial cells, protection against hypoxia/reoxygenation-induced cell death, and neutrophil adhesion.<bold>Results: </bold>Lec-SOD bound to endothelial cells with higher affinity than unmodified recombinant human superoxide dismutase (rhSOD) and significantly protected both HUVEC and HMEC-1 from cell death following 27 hours of cold hypoxia (P < 0.01). Furthermore, neutrophil adhesion to the endothelium stimulated by hypoxia and reoxygenation was significantly inhibited by treatment with lec-SOD but not by lecithin or rhSOD (P < 0.01). Analysis by flow cytometry demonstrated that E-selectin and ICAM-1 were up-regulated by hypoxia/reoxygenation that was inhibited in part by lec-SOD.<bold>Conclusions: </bold>The results from this study suggest that incorporation of lec-SOD into organ preservation solutions provides effective protection to endothelial cells against cold ischemia and reperfusion injury following transplantation.
- Subjects
CELL preservation; ENDOTHELIUM; ISCHEMIA; TREATMENT of reperfusion injuries; ANTIGENS; ANTIOXIDANTS; CELL culture; CELL death; CELL physiology; COMPARATIVE studies; CRYOPRESERVATION of organs, tissues, etc.; FLOW cytometry; FREE radicals; HYPERTONIC solutions; KIDNEY transplantation; LECITHIN; RESEARCH methodology; MEDICAL cooperation; NEUTROPHILS; REPERFUSION injury; RESEARCH; SOLUTION (Chemistry); SUPEROXIDE dismutase; EVALUATION research; UMBILICAL veins
- Publication
Kidney International, 2001, Vol 60, Issue 2, p786
- ISSN
0085-2538
- Publication type
journal article
- DOI
10.1046/j.1523-1755.2001.060002786.x