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 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.

[1]  S. Fuggle,et al.  Impact of Ischemia/Reperfusion Injury and Early Inflammatory Responses in Kidney Transplantation , 2000 .

[2]  W. Land.  Reactive oxygen species in chronic allograft dysfunction , 1999 .

[3]  D. Shoskes,et al.  Deleterious effects of delayed graft function in cadaveric renal transplant recipients independent of acute rejection. , 1998 .

[4]  D. Lefer,et al.  Modulation of leukocyte-endothelial interactions by reactive metabolites of oxygen and nitrogen: relevance to ischemic heart disease. , 1998, Free radical biology & medicine.

[5]  F. Luft,et al.  ICAM-1 antisense oligodesoxynucleotides prevent reperfusion injury and enhance immediate graft function in renal transplantation. , 1998, Kidney international.

[6]  E. Anggard,et al.  Quantification of superoxide radical formation in intact vascular tissue using a Cypridina luciferin analog as an alternative to lucigenin. , 1998, Biochemical and biophysical research communications.

[7]  M J May,et al.  NF-kappa B and Rel proteins: evolutionarily conserved mediators of immune responses. , 1998, Annual review of immunology.

[8]  R. Costa,et al.  Differential Regulation of Interleukin-8 and Intercellular Adhesion Molecule-1 by H2O2 and Tumor Necrosis Factor-α in Endothelial and Epithelial Cells* , 1997, The Journal of Biological Chemistry.

[9]  T. Aw,et al.  Molecular mechanisms of anoxia/reoxygenation-induced neutrophil adherence to cultured endothelial cells. , 1997, Circulation research.

[10]  R. Wolfe,et al.  Delayed graft function: risk factors and implications for renal allograft survival. , 1997, Transplantation.

[11]  A. Varki,et al.  Perspectives Series: Cell Adhesion in Vascular Biology Selectin Ligands: Will the Real Ones Please Stand Up? , 2022 .

[12]  A. Scheffold,et al.  P- and E-selectin mediate recruitment of T-helper-1 but not T-helper-2 cells into inflamed tissues , 1997, Nature.

[13]  D. Durand,et al.  A randomized multicenter trial comparing leukocyte function-associated antigen-1 monoclonal antibody with rabbit antithymocyte globulin as induction treatment in first kidney transplantations. , 1996, Transplantation.

[14]  B. Brenner,et al.  Antigen-independent determinants of cadaveric kidney transplant failure. , 1996, JAMA.

[15]  G S Kansas,et al.  Selectins and their ligands: current concepts and controversies. , 1996, Blood.

[16]  F. Belloc,et al.  Influence of hypoxia and hypoxia-reoxygenation on endothelial P-selectin expression. , 1996, Haemostasis.

[17]  M. Nicholson,et al.  Renal ischaemia‐reperfusion injury , 1996, The British journal of surgery.

[18]  N. Emi,et al.  Human superoxide dismutase cDNA transfection and its in vitro effect on cold preservation. , 1996, Biochemical and biophysical research communications.

[19]  T. Mayadas,et al.  Hypoxia-induced exocytosis of endothelial cell Weibel-Palade bodies. A mechanism for rapid neutrophil recruitment after cardiac preservation. , 1996, The Journal of clinical investigation.

[20]  J. Remacle,et al.  Hypoxia induces PMN adherence to umbilical vein endothelium. , 1995, Cardiovascular research.

[21]  P. Morris,et al.  Free oxygen species (FOS), FOS-scavenging enzyme P-selectin and monocyte activity in cell populations aspirated from early human renal allografts. , 1995, Transplantation proceedings.

[22]  G. Nash,et al.  Adhesion of flowing neutrophils to cultured endothelial cells after hypoxia and reoxygenation in vitro. , 1995, The American journal of physiology.

[23]  T. Peters,et al.  Cold Ischemia And Outcome In 17,937 Cadaveric Kidney Transplants , 1995, Transplantation.

[24]  L. Lasky.  Selectin-carbohydrate interactions and the initiation of the inflammatory response. , 1995, Annual review of biochemistry.

[25]  Y. Morizawa,et al.  Lecithinized superoxide dismutase enhances its pharmacologic potency by increasing its cell membrane affinity. , 1994, The Journal of pharmacology and experimental therapeutics.

[26]  G. Lutty,et al.  Determination of the mechanism of free radical generation in human aortic endothelial cells exposed to anoxia and reoxygenation. , 1994, The Journal of biological chemistry.

[27]  A. Varki,et al.  Selectin ligands. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[28]  J. Remacle,et al.  Hypoxic human umbilical vein endothelial cells induce activation of adherent polymorphonuclear leukocytes. , 1994, Blood.

[29]  J. Hakim,et al.  Reactive oxygen species rapidly increase endothelial ICAM-1 ability to bind neutrophils without detectable upregulation. , 1994, Blood.

[30]  P. Grace,et al.  Ischemia-reperfusion injury , 1994 .

[31]  G. Lutty,et al.  Measurement and characterization of free radical generation in reoxygenated human endothelial cells. , 1994, The American journal of physiology.

[32]  K. Messmer,et al.  The beneficial effect of human recombinant superoxide dismutase on acute and chronic rejection events in recipients of cadaveric renal transplants. , 1994, Transplantation.

[33]  C Michiels,et al.  Increased PMN adherence on endothelial cells after hypoxia: involvement of PAF, CD18/CD11b, and ICAM-1. , 1993, The American journal of physiology.

[34]  R. Korthuis,et al.  Reactive oxygen metabolites, neutrophils, and the pathogenesis of ischemic‐tissue/reperfusion , 1993, Clinical cardiology.

[35]  R. Colvin,et al.  A phase I trial of immunosuppression with anti-ICAM-1 (CD54) mAb in renal allograft recipients. , 1993, Transplantation.

[36]  S. Gruber,et al.  A RANDOMIZED DOUBLE‐BLIND TRIAL OF THE USE OF HUMAN RECOMBINANT SUPEROXIDE DISMUTASE IN RENAL TRANSPLANTATION , 1993, Transplantation.

[37]  R. Swerlick,et al.  HMEC-1: establishment of an immortalized human microvascular endothelial cell line. , 1992, The Journal of investigative dermatology.

[38]  Y. Morizawa,et al.  Lecithinization of superoxide dismutase potentiates its protective effect against Forssman antiserum-induced elevation in guinea pig airway resistance. , 1992, The Journal of pharmacology and experimental therapeutics.

[39]  J. Gris,et al.  Hypoxia/reoxygenation stimulates endothelium to promote neutrophil adhesion. , 1992, Free radical biology & medicine.

[40]  G. Zimmerman,et al.  Oxygen radicals induce human endothelial cells to express GMP-140 and bind neutrophils , 1991, The Journal of cell biology.

[41]  Y. Mizushima.  Lipo-prostaglandin preparations. , 1991, Prostaglandins, leukotrienes, and essential fatty acids.

[42]  S. Weiss.  Tissue destruction by neutrophils. , 1989, The New England journal of medicine.

[43]  G. Zimmerman,et al.  Hydrogen peroxide stimulates the synthesis of platelet-activating factor by endothelium and induces endothelial cell-dependent neutrophil adhesion. , 1988, The Journal of clinical investigation.

[44]  W. Maley,et al.  ABLATION OF FREE RADICAL‐MEDIATED REPERFUSION INJURY FOR THE SALVAGE OF KIDNEYS TAKEN FROM NON‐HEARTBEATING DONORS: A Quantitative Evaluation of the Proportion of Injury Caused by Reperfusion Following Periods of Warm, Cold, Combined Warm, Cold Ischemia , 1988, Transplantation.

[45]  K. Hoshi,et al.  Marked enhancement in antithrombotic activity of isocarbacyclin following its incorporation into lipid microspheres. , 1987, Prostaglandins.

[46]  G. M. Williams,et al.  The role of oxygen free radicals in mediating the reperfusion injury of cold-preserved ischemic kidneys. , 1985, Transplantation.

[47]  C. Haslett,et al.  Modulation of multiple neutrophil functions by preparative methods or trace concentrations of bacterial lipopolysaccharide. , 1985, The American journal of pathology.

[48]  R. McEver,et al.  A monoclonal antibody to a membrane glycoprotein binds only to activated platelets. , 1984, The Journal of biological chemistry.

[49]  J. McKenzie,et al.  STUDIES WITH A MONOCLONAL ANTIBODY ON THE DISTRIBUTION OF THY‐1 IN THE LYMPHOID AND EXTRACELLULAR CONNECTIVE TISSUES OF THE DOG , 1981, Transplantation.

[50]  L. Toledo-Pereyra,et al.  Clinical effect of allopurinol on preserved kidneys: a randomized double-blind study. , 1977, Annals of surgery.

[51]  E. Jaffe,et al.  Culture of human endothelial cells derived from umbilical veins. Identification by morphologic and immunologic criteria. , 1973, The Journal of clinical investigation.

[52]  I. Fridovich,et al.  Superoxide dismutase. An enzymic function for erythrocuprein (hemocuprein). , 1969, The Journal of biological chemistry.