TY - JOUR
T1 - Regulation of leukocyte function by nitric oxide donors
T2 - The effect of s-nitroso-thiol complexes
AU - Gluckman, T. L.
AU - Grossman, J. E.
AU - Folts, J. D.
AU - Kruse-Elliott, K. T.
N1 - Funding Information:
The authors give many thanks to Brett Nemke, Sarah Panzer, and Sarah Mautz for their technical assistance throughout the course of this study. This research was supported by a grant from the American Lung Association.
PY - 2000
Y1 - 2000
N2 - The aim of this study was to evaluate the effectiveness of a novel protein-bound Snitroso- 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 μM) (p < .05), but not SNAP or GSNO. Pretreatment with S-NO-alb, SNAP, or GSNO attenuated tumor necrosis factor-a 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.
AB - The aim of this study was to evaluate the effectiveness of a novel protein-bound Snitroso- 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 μM) (p < .05), but not SNAP or GSNO. Pretreatment with S-NO-alb, SNAP, or GSNO attenuated tumor necrosis factor-a 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.
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U2 - 10.1080/00984100050116753
DO - 10.1080/00984100050116753
M3 - Article
C2 - 10990160
AN - SCOPUS:0034666294
SN - 1528-7394
VL - 61
SP - 9
EP - 26
JO - Journal of Toxicology and Environmental Health - Part A
JF - Journal of Toxicology and Environmental Health - Part A
IS - 1
ER -