Relationship between calcium release and NADPH oxidase inhibition in human neutrophils

The aim of this study was to investigate the possible relationship between NADPH oxidase activity and changes in cytosolic Ca 2+ in response to different agonists. Treatment of neutrophils with leukotriene B4 (LTB 4) demonstrated characteristic changes to cytoslic Ca 2+ yielding an EC 50 of 4 nM. Th...

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Bibliographic Details
Published in:Biochemical and biophysical research communications 2009-06, Vol.384 (1), p.87-92
Main Authors: Salmon, Michael D., Ahluwalia, Jatinder
Format: Article
Language:English
Subjects:
Calcium - metabolism
Calcium release
Cells, Cultured
Depolarisation
Fatty Alcohols - pharmacology
Glycols - pharmacology
Humans
Leukotriene Antagonists - pharmacology
Leukotriene B4 (LTB 4)
N-formyl- l-methionyl- l-leucyl- l-phenylalanine (FMLP)
N-Formylmethionine Leucyl-Phenylalanine - pharmacology
NADPH oxidase
NADPH Oxidases - antagonists & inhibitors
NADPH Oxidases - metabolism
Neutrophils
Neutrophils - drug effects
Neutrophils - enzymology
Neutrophils - metabolism
Platelet activating factor (PAF)
Receptors, Leukotriene B4 - antagonists & inhibitors
Receptors, Leukotriene B4 - metabolism
Tetradecanoylphorbol Acetate - pharmacology
Tetrazoles - pharmacology
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Summary:The aim of this study was to investigate the possible relationship between NADPH oxidase activity and changes in cytosolic Ca 2+ in response to different agonists. Treatment of neutrophils with leukotriene B4 (LTB 4) demonstrated characteristic changes to cytoslic Ca 2+ yielding an EC 50 of 4 nM. The pA 2 values for the specific LTB 4 receptor (BLT) antagonists, U-75302 and LY-255283 were 6.32 and 6.38, respectively. Similarly, neutrophils treated with N-formyl- l-methionyl- l-leucyl- l-phenylalanine (FMLP) and platelet activating factor (PAF) exhibited changes in cytoslic Ca 2+ in a dose dependant manner with pD 2 values of 9.0 and 9.9, respectively. The phorbol ester PMA prevented elevations in cytosolic Ca 2+ in response to LTB 4, FMLP and PAF with IC 50 values of 5.88, 1.44 and 5.71 nM, respectively. In addition, potent NADPH oxidase inhibitors apocynin and diphenyleneiodonium (DPI) inhibited FMLP mediated cytosolic Ca 2+ release. These results demonstrate that inhibition of the NADPH oxidase suppresses cytosolic Ca 2+ release in FMLP activated human neutrophils.
ISSN:0006-291X
1090-2104
DOI:10.1016/j.bbrc.2009.04.079