Priming action of inositol hexakisphosphate (InsP6) on the stimulated respiratory burst in human neutrophils

Abstract After priming by a number of different host, bacterial and chemical agents, human neutrophils may be stimulated to produce a greater respiratory burst than would be elicited by the stimulus alone. Other neutrophil functions may be similarly enhanced by pre-exposure to a priming agent. We describe here a new extracellular role for inositol hexakisphosphate (InsP 6 ) as a priming agent for a variety of human neutrophil functional responses. Preincubation of the cells with InsP 6 alone (up to 250 μM) has no stimulatory effect upon the basal production of reactive oxygen intermediates but the response to a subsequent stimulus (FMLP, PMA or phagocytic particles) is substantially enhanced. Levels 100–200% higher than ‘stimulus only’ controls have been recorded. Peak enhancement of the FMLP-induced oxidative response occurs after 1–2 min preincubation with InsP 6 and the effect is dose-dependent (maximum at approx. 100 μM InsP 6 ). As others have shown FMLP stimulation of superoxide anion production has no external Ca 2+ dependence but the presence of low levels of Ca 2+ and Mg 2+ (0.1 mM) during priming appears to be an essential requirement for full expression. Reports of intracellular concentrations of InsP 6 in mammalian cells in the 30–100 μM range suggest that the local release of this inositol polyphosphate from damaged or effete cells could have a physiologically important modulatory role on neutrophil functions.