Nitrous oxide impairs the neutrophil oxidative response.
BACKGROUND
Nitrous oxide has been shown inconsistently to impair the oxidative function of neutrophils. The choice of the stimulus, receptor agonists, or stimuli acting independent of receptors seems to determine whether nitrous oxide impairs the oxidative functions, suggesting an interference with the cytosolic signaling of neutrophils.


METHODS
Production of hydrogen peroxide by neutrophils was assessed using flow cytometric analysis. N-formyl-methionyl-leucyl-phenylalanine (FMLP), C5a, dioctanylglycerol, and phorbol-12-myristate-13-acetate were used as stimuli. In addition, the expression of receptors for FMLP and the cytosolic-free calcium response of cells were measured.


RESULTS
Nitrous oxide depresses C5a- or FMLP-induced generation of reactive oxygen derivatives in a concentration-dependent manner. However, the response with direct activation of protein kinase C was unaffected. Further, the number of FMLP receptors and the cytosolic calcium response were unaffected. Inhibition of the oxidative response was not reversible within the observation period of 4 h.


CONCLUSIONS
Nitrous oxide inhibited the intracellular signaling of the investigated G-protein-coupled receptors for chemotactic peptides. No interference of nitrous oxide with reduced nicotinamide adenine dinucleotide phosphate oxidase, the oxidative enzyme system of neutrophils, nor with its activation through protein kinase C was detected.
Fröhlich
D
D
Department of Anesthesiology, University of Regensburg, Germany. dieter.froehlich@klinik.uni-regensburg.de
Rothe
G
G
Wittmann
S
S
Schmitz
G
G
Schmid
P
P
Taeger
K
K
Hobbhahn
J
J
D000328:Adult; D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D005434:Flow Cytometry; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism; D009609:Nitrous Oxide / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D018000:Receptors, Peptide / Q000378:metabolism; D016897:Respiratory Burst / Q000187:drug effects*; D015290:Second Messenger Systems / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D018685:Anesthetics, Inhalation; D017382:Reactive Oxygen Species; D018000:Receptors, Peptide; D009240:N-Formylmethionine Leucyl-Phenylalanine; D006861:Hydrogen Peroxide; D009609:Nitrous Oxide; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium