Inhibition by nitric oxide-releasing compounds of E-selectin expression in and neutrophil adhesion to human endothelial cells.
The effects of two chemically unrelated nitric oxide (NO)-releasing compounds were studied on adhesion molecule expression in and neutrophil adhesion to human umbilical vein endothelial cells. Incubation of confluent monolayers of endothelial cells with increasing concentrations of lipopolysaccharide stimulated the adhesion of polymorphonuclear leukocytes to endothelial cells. Flow cytometric analysis showed that lipopolysaccharide treatment upregulated the expression of adhesion molecules E-selectin and intercellular adhesion molecule-1 (ICAM-1) in human umbilical vein endothelial cells. A novel NO-releasing compound GEA 3175 (1,2,3, 4-oxatriazolium, -3-(3-chloro-2-methylphenyl)-5-[[(4-methylphenyl)sulfonyl]amino]-, hydroxide inner salt) inhibited lipopolysaccharide-induced adhesion being more potent than the earlier known NO donor S-nitroso-N-acetylpenicillamine. The increased E-selectin expression induced by lipopolysaccharide was significantly attenuated by the two NO donors tested whereas ICAM-1 expression remained unaltered. The present data show that NO donors inhibit E-selectin expression in and neutrophil adhesion to lipopolysaccharide-stimulated vascular endothelial cells. Thus, by inhibiting leukocyte adhesion NO donors may reduce leukocyte infiltration and leukocyte-mediated tissue injury in inflammation and ischemia-reperfusion injury.
Kosonen
O
O
Medical School, University of Tampere FIN-33014, Tampere, Finland.
Kankaanranta
H
H
Uotila
J
J
Moilanen
E
E
D002448:Cell Adhesion / Q000187:drug effects; D002478:Cells, Cultured; D019040:E-Selectin / Q000096:biosynthesis*; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000502:physiology; D008070:Lipopolysaccharides / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects* / Q000502:physiology; D009569:Nitric Oxide / Q000502:physiology*; D020030:Nitric Oxide Donors / Q000494:pharmacology*; D019323:omega-N-Methylarginine / Q000494:pharmacology
D019040:E-Selectin; D008070:Lipopolysaccharides; D020030:Nitric Oxide Donors; D018799:Intercellular Adhesion Molecule-1; D019323:omega-N-Methylarginine; D009569:Nitric Oxide