Enhancement of neutrophil response by SH-containing compounds: Modulation of superoxide and hydrogen peroxide production

Rajkovic, I. A.

doi:10.1016/0006-2952(84)90177-1

Cited by 13 publications

(1 citation statement)

References 29 publications

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“…The lack of development of infectious symptoms or signs also argues that reduction of the oxidant burden in CF is not associated with inhibition of CF host defense against microorganisms, a potentially serious problem in the chronically colonized milieu in the CF lower respiratory tract. This is consistent with the finding that, in vitro, extracellular GSH concentrations of up to 300 µM do not inhibit bactericidal or phagocytic ability of neutrophils (26). Moreover, because deficiency of GSH has been associated with abnormal phagocytic cell function (10,23,32,39) and, in vitro, increased extracellular GSH prevents exogenous oxidant-induced intracellular GSH depletion and decreased phagocytic capacity by neutrophils (27), augmentation of ELF GSH levels by aerosol therapy would be expected to improve antibacterial function on the respiratory epithelial surface in CF.…”

Section: Discussionsupporting

confidence: 92%

Glutathione aerosol suppresses lung epithelial surface inflammatory cell-derived oxidants in cystic fibrosis

Roum

Borok

McElvaney

et al. 1999

Journal of Applied Physiology

103

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Cystic fibrosis (CF) is characterized by accumulation of activated neutrophils and macrophages on the respiratory epithelial surface (RES); these cells release toxic oxidants, which contribute to the marked epithelial derangements seen in CF. These deleterious consequences are magnified, since reduced glutathione (GSH), an antioxidant present in high concentrations in normal respiratory epithelial lining fluid (ELF), is deficient in CF ELF. To evaluate the feasibility of increasing ELF GSH levels and enhancing RES antioxidant protection, GSH aerosol was delivered (600 mg twice daily for 3 days) to seven patients with CF. ELF total, reduced, and oxidized GSH increased (P < 0.05, all compared with before GSH therapy), suggesting adequate RES delivery and utilization of GSH. Phorbol 12-myristate 13-acetate-stimulated superoxide anion (O2-.) release by ELF inflammatory cells decreased after GSH therapy (P < 0.002). This paralleled observations that GSH added in vitro to CF ELF inflammatory cells suppressed O2-. release (P < 0.001). No adverse effects were noted during treatment. Together, these observations demonstrate the feasibility of using GSH aerosol to restore RES oxidant-antioxidant balance in CF and support the rationale for further clinical evaluation.

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Section: Discussionsupporting

confidence: 92%

Glutathione aerosol suppresses lung epithelial surface inflammatory cell-derived oxidants in cystic fibrosis

Roum

Borok

McElvaney

et al. 1999

Journal of Applied Physiology

103

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Abnormalities of Neutrophil Phagocytosis, Intracellular Killing and Metabolic Activity in Alcoholic Cirrhosis and Hepatitis

Rajkovic¹,

Williams²

1986

Hepatology

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252

163

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Neutrophil functions of phagocytosis and intracellular killing of bacteria were examined in 40 patients with alcoholic cirrhosis of whom 18 had a superimposed acute alcoholic hepatitis. In 65% of these, defective neutrophil phagocytosis was demonstrable, and in 62.5% there was a defect of intracellular killing of either Staphylococcus aureus or Escherichia coli. Studies of the patients' serum failed to reveal inhibitors of neutrophil function. Additional assays of superoxide (O2-) and hydrogen peroxide production, hexose monophosphate shunt activity, degranulation and cellular levels of granule enzymes and glutathione revealed that these neutrophil defects are caused by both reduced production of superoxide and defects of degranulation. The hydrogen peroxide/superoxide molar ratio was raised in patients' neutrophils, and the strong inverse correlation found between the value of this ratio and intracellular levels of reduced glutathione would be consistent with the hypothesis that the neutrophils from patients with cirrhosis are unable to detoxify hydrogen peroxide effectively and that this is a result of reduced levels of glutathione in the cells. The consequent increase in oxidant stress, both intra- and extracellularly, may be the cause of phagocytic and degranulation defects. The reduced responses of patients' neutrophils may be caused by previous exposure of the cells to activating stimuli in circulation, as evidenced by depleted intracellular levels of granule enzymes and glutathione. Neutrophils from the patients with a superimposed acute alcoholic hepatitis had depressed phagocytosis in the early stages of incubation but, on the whole, neutrophils from these patients had a greater capacity for ingestion and killing of bacteria than neutrophils from patients with cirrhosis alone.(ABSTRACT TRUNCATED AT 250 WORDS)

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Exogenous Nitric Oxide Can Trigger a Preconditioned State Through a Free Radical Mechanism, But Endogenous Nitric Oxide Is Not a Trigger of Classical Ischemic Preconditioning

Nakano

Liu

Heusch

et al. 2000

Journal of Molecular and Cellular Cardiology

161

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Enhancement of neutrophil response by SH-containing compounds: Modulation of superoxide and hydrogen peroxide production

Cited by 13 publications

References 29 publications

Glutathione aerosol suppresses lung epithelial surface inflammatory cell-derived oxidants in cystic fibrosis

Glutathione aerosol suppresses lung epithelial surface inflammatory cell-derived oxidants in cystic fibrosis

Abnormalities of Neutrophil Phagocytosis, Intracellular Killing and Metabolic Activity in Alcoholic Cirrhosis and Hepatitis

Exogenous Nitric Oxide Can Trigger a Preconditioned State Through a Free Radical Mechanism, But Endogenous Nitric Oxide Is Not a Trigger of Classical Ischemic Preconditioning

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