Abstract
It has long been assumed that a rise in cytosolic free Ca2+, [Ca2+]i, is a necessary and sufficient event for the stimulation of a variety of cellular processes1,2. The development of a technique which allows monitoring of [Ca2+]i in small intact cells3 has led to a critical revision of this simple postulate4–7. We have recently shown that in neutrophils, Ca2+-ionophore-induced elevations of [Ca2+]i, quantitatively similar to those caused by chemotatic peptides, are ineffective in stimulating cell responses8, which suggests that an additional signal is required for receptor-mediated activation. Here we show that subthreshold concentrations of phorbol myristate acetate (PMA) and of a Ca2+ ionophore can quantitatively mimic the effect of a physiological agonist. However, PMA at higher concentrations can trigger NADPH-oxidase activity, exocytosis and protein phosphorylation, even when [Ca2+]i is lowered 10–20 times below the normal resting level. These results strongly suggest that activation of protein kinase C is sufficient, by itself, to induce NADPH-oxidase activation and exocytosis of secondary granules in neutrophils.
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Di Virgilio, F., Lew, D. & Pozzan, T. Protein kinase C activation of physiological processes in human neutrophils at vanishingly small cytosolic Ca2+ levels. Nature 310, 691–693 (1984). https://doi.org/10.1038/310691a0
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DOI: https://doi.org/10.1038/310691a0
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