Endothelial cell protection against ischemia/reperfusion injury by lecithinized superoxide dismutase.
BACKGROUND: 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 affini...
Main Authors: | , , , , , , , |
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Format: | Journal article |
Language: | English |
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2001
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author | Koo, D Welsh, K West, N Channon, K Penington, A Roake, J Morris, P Fuggle, S |
author_facet | Koo, D Welsh, K West, N Channon, K Penington, A Roake, J Morris, P Fuggle, S |
author_sort | Koo, D |
collection | OXFORD |
description | BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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. |
first_indexed | 2024-03-07T04:43:56Z |
format | Journal article |
id | oxford-uuid:d297d3f5-2440-4194-b458-713e56cdc740 |
institution | University of Oxford |
language | English |
last_indexed | 2024-03-07T04:43:56Z |
publishDate | 2001 |
record_format | dspace |
spelling | oxford-uuid:d297d3f5-2440-4194-b458-713e56cdc7402022-03-27T08:05:09ZEndothelial cell protection against ischemia/reperfusion injury by lecithinized superoxide dismutase.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:d297d3f5-2440-4194-b458-713e56cdc740EnglishSymplectic Elements at Oxford2001Koo, DWelsh, KWest, NChannon, KPenington, ARoake, JMorris, PFuggle, SBACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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. |
spellingShingle | Koo, D Welsh, K West, N Channon, K Penington, A Roake, J Morris, P Fuggle, S Endothelial cell protection against ischemia/reperfusion injury by lecithinized superoxide dismutase. |
title | Endothelial cell protection against ischemia/reperfusion injury by lecithinized superoxide dismutase. |
title_full | Endothelial cell protection against ischemia/reperfusion injury by lecithinized superoxide dismutase. |
title_fullStr | Endothelial cell protection against ischemia/reperfusion injury by lecithinized superoxide dismutase. |
title_full_unstemmed | Endothelial cell protection against ischemia/reperfusion injury by lecithinized superoxide dismutase. |
title_short | Endothelial cell protection against ischemia/reperfusion injury by lecithinized superoxide dismutase. |
title_sort | endothelial cell protection against ischemia reperfusion injury by lecithinized superoxide dismutase |
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