REGULATION OF LEUKOCYTE FUNCTION BY NITRIC OXIDE DONORS: THE EFFECT OF S-NITROSO-THIOL COMPLEXES

• Published in: Journal of Toxicology and Environmental Health, Part A Part A, 2000-09, Vol.61 (1), p.9-26
• Main Authors: Gluckman, T L, Grossman, J E, Folts, J D, Kruse-Elliott, K T
• Format: Article
• Language: English
• Subjects: Biological and medical sciences; Cell Adhesion - drug effects; Endothelium, Vascular - cytology; Endothelium, Vascular - drug effects; Endothelium, Vascular - metabolism; Enzyme Inhibitors - pharmacology; Fundamental and applied biological sciences. Psychology; Glutathione - analogs & derivatives; Glutathione - pharmacology; Humans; In Vitro Techniques; Indicators and Reagents; Inflammation; Kinetics; Leukocytes - drug effects; Lipopolysaccharides - pharmacology; Molecular and cellular biology; Neutrophils - drug effects; Neutrophils - metabolism; Nitric Oxide Donors - pharmacology; Nitric Oxide Synthase - antagonists & inhibitors; Nitroso Compounds - pharmacology; Oxygen Consumption - drug effects; Penicillamine - analogs & derivatives; Penicillamine - pharmacology; S-Nitroso-N-Acetylpenicillamine; S-Nitrosoglutathione; Serum Albumin, Bovine - pharmacology; Sulfhydryl Compounds - pharmacology; Tumor Necrosis Factor-alpha - pharmacology
• ISSN: 1528-7394; 0098-4108; 1087-2620
• DOI: 10.1080/00984100050116753

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.