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Ulex europaeus agglutinin II (UEA-II) is a novel, potent inhibitor of complement activation

¹ Center for Experimental Therapeutics and Reperfusion Injury, Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA
² Department of Emergency Medicine, Beth Israel-Deaconess Hospital, Boston, Massachusetts 02118, USA

Reprint requests to: Gregory L. Stahl, Ph.D., Center for Experimental Therapeutics and Reperfusion Injury, Department of Anesthesia, Brigham & Women's Hospital, Harvard Medical School, 75 Francis Street, Boston, MA 02115 USA; e-mail: gstahl{at}zeus.bwh.harvard.edu; fax: (617) 278-6957.

Complement is an important mediator of vascular injury following oxidative stress. We recently demonstrated that complement activation following endothelial oxidative stress is mediated by mannose-binding lectin (MBL) and activation of the lectin complement pathway. Here, we investigated whether nine plant lectins which have a binding profile similar to that of MBL competitively inhibit MBL deposition and subsequent complement activation following human umbilical vein endothelial cell (HUVEC) oxidative stress. HUVEC oxidative stress (1% O₂, 24 hr) significantly increased Ulex europaeus agglutinin II (UEA-II) binding by 72 ± 9% compared to normoxic cells. UEA-II inhibited MBL binding to HUVEC in a concentration-dependent manner following oxidative stress. Further, MBL inhibited UEA-II binding to HUVEC in a concentration-dependent manner following oxidative stress, suggesting a common ligand. UEA-II ( 100 µmol/L) did not attenuate the hemolytic activity, nor did it inhibit C3a des Arg formation from alternative or classical complement pathway-specific hemolytic assays. C3 deposition (measured by ELISA) following HUVEC oxidative stress was inhibited by UEA-II in a concentration-dependent manner (IC₅₀ = 10 pmol/L). UEA-II inhibited C3 and MBL co-localization (confocal microscopy) in a concentration-dependent manner on HUVEC following oxidative stress (IC₅₀ 1 pmol/L). Finally, UEA-II significantly inhibited complement-dependent neutrophil chemotaxis, but failed to inhibit fMLP-mediated chemotaxis, following endothelial oxidative stress. These data demonstrate that UEA-II is a novel, potent inhibitor of human MBL deposition and complement activation following human endothelial oxidative stress.

Keywords: Hypoxia; reoxygenation; mannose-binding lectin; neutrophils; chemotaxis

Abbreviations: fMLP, formyl methionine leucine phenylalanine • GlcNAc, N-acetylglucosamine • GVB, gelatin veronal buffer • HRP, horseradish peroxidase • HS, human serum • HUVEC, human umbilical vein endothelial cells • mAb, monoclonal antibody • MBL, mannose-binding lectin • pAb, polyclonal antibody • UEA-II, Ulex europaeus agglutinin II.

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