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 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