Regulation of leukocyte function by nitric oxide donors: the effect of S-nitroso-thiol complexes.
The aim of this study was to evaluate the effectiveness of a novel protein-bound S-nitroso-thiol, S-nitroso-albumin (S-NO-alb), in modulating neutrophil-endothelial cell adhesion, activation, and interactions. Due to the highly variable kinetics of NO release from the low-molecular-weight thiol adducts S-nitroso-N-acetylpenicillamine (SNAP) and S-nitroso-glutathione (GSNO), we expected S-NO-alb to be a more effective modulator of inflammatory interactions through its slow, steady, and prolonged release of NO. Human umbilical-vein endothelial cells (HUVECs) challenged with lipopolysaccharide (LPS) demonstrated upregulated adhesion of neutrophils that was significantly attenuated by pretreatment with S-NO-alb (1.0-100 microM) (p < .05), but not SNAP or GSNO. Pretreatment with S-NO-alb, SNAP, or GSNO attenuated tumor necrosis factor-alpha primed *O2- release from neutrophils and increased neutrophil cGMP accumulation. On a molar basis, S-NO-alb expressed a 10-fold greater potency than SNAP or GSNO at modulating these effects. Kinetics studies confirmed the relative stability of spontaneous NO release from S-NO-alb compared with highly variable kinetic profiles of SNAP and GSNO. Our results demonstrate that S-NO-alb more effectively modulates endothelial-cell and neutrophil immunoinflammatory responses versus its related low-molecular-weight thiol complexes.
Gluckman
T L
TL
Department of Surgical Sciences, University of Wisconsin, Madison 53706, USA.
Grossman
J E
JE
Folts
J D
JD
Kruse-Elliott
K T
KT
D002448:Cell Adhesion / Q000187:drug effects; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005978:Glutathione / Q000031:analogs & derivatives / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D007202:Indicators and Reagents; D007700:Kinetics; D007962:Leukocytes / Q000187:drug effects*; D008070:Lipopolysaccharides / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism; D020030:Nitric Oxide Donors / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D009603:Nitroso Compounds / Q000494:pharmacology*; D010101:Oxygen Consumption / Q000187:drug effects; D010396:Penicillamine / Q000031:analogs & derivatives / Q000494:pharmacology; D026423:S-Nitroso-N-Acetylpenicillamine; D026422:S-Nitrosoglutathione; D012710:Serum Albumin, Bovine / Q000494:pharmacology; D013438:Sulfhydryl Compounds / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D004791:Enzyme Inhibitors; D007202:Indicators and Reagents; D008070:Lipopolysaccharides; D020030:Nitric Oxide Donors; D009603:Nitroso Compounds; C091665:S-nitrosoalbumin; D013438:Sulfhydryl Compounds; D014409:Tumor Necrosis Factor-alpha; D012710:Serum Albumin, Bovine; D026422:S-Nitrosoglutathione; D026423:S-Nitroso-N-Acetylpenicillamine; D019001:Nitric Oxide Synthase; D005978:Glutathione; D010396:Penicillamine