IFN-γ Induces Calcium Transients and Increases the Capacitative Calcium Entry in Human Neutrophils

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Abstract
We have previously reported that long-term priming of human polymorphonuclear neutrophilic granulocytes (PMN) with interferon-γ (IFN-γ) increased the fMLP-stimulated calcium influx. We now show that also after short-term incubation with IFN-γ, PMN calcium metabolism is modulated. Single adherent cells in three different calcium-containing buffers (high, normal, and low [Ca2+]) were stimulated with the bacterial peptide fMLP or the Ca-ATPase inhibitor thapsigargin (Tg) after about 5 min preincubation with IFN-γ. The results of this protocol indicated that IFN-γ increases both calcium influx and calcium sequestration. Store dependent Ca2+ influx, directly measured on readdition of calcium to Tg-treated cells incubated in EGTA buffer, was significantly enhanced in IFN-γ-treated cells. This effect of IFN-γ was enhanced by the tyrosine kinase inhibitor herbimycin A. Strikingly, in low extracellular calcium concentrations, IFN-γ induced calcium transients in 20%-60% of the cells. The proportion of PMN responding with Ca2+ transients increased with decreasing extracellular calcium concentration. Average lagtime from addition of IFN-γ to a response that could be measured was 7.3 sec, and average increase in [Ca2+] above the basal level was 790 nM. These IFN-γ-induced transients could not be depressed by herbimycin A. Thus, IFN-γ can increase capacitative calcium influx, induce calcium transients, and possibly affect calcium sequestration in human PMN.