Endothelial cell protection against ischemia/reperfusion injury by lecithinized superoxide dismutase

Background Organs used for transplantation may experience long periods of c old ischemic preservation and consequently oxygen free radical-mediated dam age following reperfusion. Lecithinized superoxide dismutase (lec-SOD) is a novel Free radical scavenger that has been shown to bind with high affinit y 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. Methods. An in vitro study was performed on large vessel endothelial cells (HUVEC) and a human microvascular endothelial cell line HMEC-1. to investig ate 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/reoxgenation-induced cell death. and neutrophil adhesion. Results. Lec-SOD bound to endothelial cells with higher affinity than unmod ified recombinant human superoxide dismutase (rhSOD) and significantly prot ected both HUVEC and HMEC-1 from cell death following 27 hours of cold hypo xia (P < 0.01). Furthermore, neutrophil adhesion to the endothelium stimula ted by hypoxia a < nd reoxygenation was significantly inhibited by treatmen t with lec-SOD but not by lecithin or rhSOD (P 0.01). Analysis by flow cyto metry demonstrated that E-selectin and ICAM-1 were up-regulated by hypoxia/ reoxygenation that was inhibited in part by lec-SOD. Conclusions. The results from this study suggest that incorporation of lec- SOD into organ preservation solutions provides effective protection to endo thelial cells against cold ischemia and reperfusion injury following transp lantation.