Ulex europaeus agglutinin II (UEA-II) is a novel, potent inhibitor of complement activation.
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% O(2), 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 (< or = 100 micromol/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 (IC(50) = 10 pmol/L). UEA-II inhibited C3 and MBL co-localization (confocal microscopy) in a concentration-dependent manner on HUVEC following oxidative stress (IC(50) approximately 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.
Lekowski
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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.
Collard
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Reenstra
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Stahl
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D001667:Binding, Competitive; D003167:Complement Activation; D015926:Complement C3a / Q000378:metabolism; D003165:Complement System Proteins / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000166:cytology; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D000860:Hypoxia; D020128:Inhibitory Concentration 50; D037102:Lectins / Q000737:chemistry* / Q000378:metabolism; D008024:Ligands; D018613:Microscopy, Confocal; D009504:Neutrophils / Q000378:metabolism; D018384:Oxidative Stress; D037121:Plant Lectins; D011485:Protein Binding; D019685:Rosales / Q000737:chemistry*; D014471:Umbilical Veins / Q000166:cytology
D037102:Lectins; D008024:Ligands; D037121:Plant Lectins; D015926:Complement C3a; D003165:Complement System Proteins