Control of interleukin-18 secretion by dendritic cells: role of calcium influxes

Here we show that dendritic cells accumulate the precursor form of the lead erless secretory protein interleukin-18 (pro-interleukin-18) in the cell cy tosol and in organelles cofractionating with endolysosomes. Upon antigen sp ecific contact with T lymphocytes, particulated pro-interleukin-18 decrease s rapidly, and the cytokine appears extracellularly, suggesting that exocyt osis of pro-interleukin-18-containing organelles is induced. Exocytosis of secretory lysosomes is modulated by calcium: in agreement with this, calciu m influx results in secretion of prointerleukin-18. In turn, pro-interleuki n-18 secretion induced by T cells is prevented by the calcium channel block er nifedipine, Our results demonstrate a novel, calcium-mediated mechanism of post-translational regulation of secretion for interleukin-18, that allo ws a fast release of the cytokine. (C) 2000 Federation of European Biochemi cal Societies. Published by Elsevier Science B.V. All rights reserved.