Regulation of leukocyte function by nitric oxide donors: The effect of s-nitroso-thiol complexes

T. L. Gluckman, J. E. Grossman, J. D. Folts, K. T. Kruse-Elliott

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)9-26
Number of pages18
JournalJournal of Toxicology and Environmental Health - Part A
Volume61
Issue number1
DOIs
StatePublished - Jan 1 2000

ASJC Scopus subject areas

  • Toxicology
  • Health, Toxicology and Mutagenesis

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