Relationship of phosphatidylinositol bisphosphate hydrolysis to calcium mobilization and functional activation in fluoride-treated neutrophils

Sodium fluoride (20 mM) effected rapid hydrolysis of phosphatidylinositol bisphosphate (PIP2) in human neutrophils. Intracellular free Ca2+ levels increased after PIP2 hydrolysis but before respiratory burst activation. Both the increase in intracellular free Ca2+ levels and the extent of functional...

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Bibliographic Details
Published in:The Journal of clinical investigation 1987-07, Vol.80 (1), p.145-153
Main Authors: ENGLISH, D, DEBONO, D. J, GABIG, T. G
Format: Article
Language:English
Subjects:
Applied sciences
calcium
Calcium - blood
Cell Membrane - metabolism
Cytosol - metabolism
Exact sciences and technology
fluoride
Humans
Hydrolysis
Kinetics
leukocytes (neutrophilic)
man
Neutrophils - drug effects
Neutrophils - metabolism
Other techniques and industries
Oxidation-Reduction
Phosphatidylinositol 4,5-Diphosphate
phosphatidylinositol bisphosphate
Phosphatidylinositol Phosphates
Phosphatidylinositols - blood
Phospholipids - blood
Sodium Fluoride - pharmacology
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Summary:Sodium fluoride (20 mM) effected rapid hydrolysis of phosphatidylinositol bisphosphate (PIP2) in human neutrophils. Intracellular free Ca2+ levels increased after PIP2 hydrolysis but before respiratory burst activation. Both the increase in intracellular free Ca2+ levels and the extent of functional activation were dependent on the availability of extracellular Ca2+. The rate of F(-)-stimulated PIP2 hydrolysis, however, was not affected when the rise in cytosolic Ca2+ was severely limited by depletion of extracellular Ca2+. Fluoride caused the specific hydrolysis of PIP2 in isolated neutrophil plasma membranes. This effect occurred in the presence of low levels of available Ca2+ and was accompanied by the release of inositol phosphates. We conclude that PIP2 hydrolysis is an early event in the response of neutrophils to F-. This response is not Ca2+-regulated but may lead to an influx of Ca2+ from the extracellular medium. Activation of a PIP2-specific phospholipase independent of a change in cytosolic free Ca2+ levels may be the initial event in the stimulus-response pathway triggered by fluoride.
ISSN:0021-9738
1558-8238
DOI:10.1172/JCI113040