The effect of hypochlorous acid on the expression of adhesion molecules and activation of NF-kappaB in cultured human endothelial cells.
Exposure to oxidants can up-regulate the expression of adhesion molecules in endothelial cells with a consequent increase in neutrophil attachment. Similarly, the transcription factor nuclear factor-kappaB (NF-kappaB), which controls the expression of the intercellular adhesion molecules (ICAMs), can also be activated by oxidants in some cells. We have investigated whether hypochlorous acid (HOCl), the major strong oxidant produced by neutrophils, can affect the expression of adhesion molecules on human umbilical vein endothelial cells (HUVEC) and promote neutrophil adhesion. We found that HOCl could induce an increase in neutrophil adhesion to the endothelial cells after 60 min of treatment. Activation of NF-kappaB could be detected under similar conditions. However, the dose of HOCl required for this effect resulted in considerable longer-term toxicity to the cells. Treatment of HUVEC with sublethal doses of HOCl had no effect on NF-kappaB activation, neutrophil adhesion, or the surface expression of E-selectin, ICAM-1, or P-selectin. However, pretreatment with low concentrations of HOCl prevented phorbol myristate acetate-induced von Willebrand factor expression (a marker for P-selectin). These results show that, unlike H(2)O(2), HOCl does not significantly enhance neutrophil attachment to the endothelium. Rather it may be able to inhibit the expression of adhesion molecules with important consequences for endothelial function and inflammatory vascular disease.
Pullar
Juliet M
JM
Free Radical Research Group, Department of Pathology, Christchurch School of Medicine and Health Sciences, P.O. Box 4345, Christchurch, New Zealand. juliet.pullar@chmeds.ac.nz
Winterbourn
Christine C
CC
Vissers
Margret C M
MC
D002448:Cell Adhesion; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D019040:E-Selectin / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology*; D004789:Enzyme Activation; D006801:Humans; D006997:Hypochlorous Acid / Q000494:pharmacology*; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D008856:Microscopy, Fluorescence; D016328:NF-kappa B / Q000378:metabolism*; D009504:Neutrophils / Q000378:metabolism; D010100:Oxygen / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013997:Time Factors; D014471:Umbilical Veins / Q000166:cytology; D015854:Up-Regulation; D014841:von Willebrand Factor / Q000378:metabolism
D019040:E-Selectin; D016328:NF-kappa B; D014841:von Willebrand Factor; D018799:Intercellular Adhesion Molecule-1; D006997:Hypochlorous Acid; D013755:Tetradecanoylphorbol Acetate; D010100:Oxygen