Nitrous oxide impairs the neutrophil oxidative response

Area of Science:

• Immunology
• Cellular Biology
• Pharmacology

Background:

• Nitrous oxide's effect on neutrophil oxidative function is inconsistent.
• The type of stimulus used appears to influence whether nitrous oxide impairs oxidative functions.
• This suggests nitrous oxide may interfere with neutrophil cytosolic signaling.

Purpose of the Study:

• To investigate the effect of nitrous oxide on neutrophil oxidative function.
• To determine if nitrous oxide interferes with specific signaling pathways in neutrophils.
• To elucidate the mechanism by which nitrous oxide affects neutrophil responses.

Main Methods:

• Neutrophil hydrogen peroxide production was measured using flow cytometry.
• Stimuli included N-formyl-methionyl-leucyl-phenylalanine (FMLP), C5a, dioctanylglycerol, and phorbol-12-myristate-13-acetate.
• FMLP receptor expression and cytosolic calcium response were also assessed.

Main Results:

• Nitrous oxide concentration-dependently reduced C5a- and FMLP-induced reactive oxygen derivative generation.
• Direct activation of protein kinase C did not affect the oxidative response.
• FMLP receptor expression and cytosolic calcium response remained unaffected.
• The observed inhibition was not reversible within a 4-hour observation period.

Conclusions:

• Nitrous oxide inhibits intracellular signaling of G-protein-coupled receptors for chemotactic peptides.
• Nitrous oxide does not interfere with reduced nicotinamide adenine dinucleotide phosphate oxidase, the neutrophil's oxidative enzyme system.
• No interference was detected with protein kinase C-mediated activation of the oxidative response.