Scientific article

Store-operated Ca2+ influx and stimulation of exocytosis in HL-60 granulocytes

Published inThe Journal of biological chemistry, vol. 272, no. 45, p. 28360-28367
Publication date1997

This study addresses the role of store-operated Ca2+ influx in the regulation of exocytosis in inflammatory cells. In HL-60 granulocytes, which do not possess voltage-operated Ca2+ channels, the chemotactic peptide fMet-Leu-Phe (fMLP) was able to stimulate store-operated Ca2+ influx and to trigger exocytosis of primary granules. An efficient triggering of exocytosis by fMLP required the presence of extracellular Ca2+ and was inhibited by blockers of store-operated Ca2+ influx. However, receptor-independent activation of store-operated Ca2+ influx through thapsigargin did not trigger exocytosis. fMLP was unable to stimulate exocytosis in the absence of cytosolic free Ca2+ concentration [Ca2+]c elevations. However, a second signal generated by fMLP synergized with store-operated Ca2+ influx to trigger exocytosis and led to a left shift of the exocytosis/[Ca2+]c relationship in ionomycin-stimulated cells. The synergistic fMLP-generated signaling cascade was long-lasting, involved a pertussis toxin-sensitive G protein and a phosphatidylinositol 3-kinase. In summary, store-operated Ca2+ influx is crucial for the efficient triggering of exocytosis in HL-60 granulocytes, but, as opposed to Ca2+ influx through voltage-operated Ca2+ channels in neurons, it is not a sufficient stimulus by itself and requires synergistic receptor-generated signals.

  • Androstadienes/pharmacology
  • Calcium/ metabolism
  • Cytoplasmic Granules/drug effects/metabolism
  • Drug Synergism
  • Enzyme Activation
  • Enzyme Inhibitors/pharmacology
  • Estrenes/pharmacology
  • Exocytosis/drug effects
  • GTP-Binding Proteins/metabolism
  • Genistein/pharmacology
  • Granulocytes/cytology/drug effects/ metabolism
  • HL-60 Cells
  • Humans
  • N-Formylmethionine Leucyl-Phenylalanine/pharmacology
  • Pertussis Toxin
  • Phosphodiesterase Inhibitors/pharmacology
  • Phospholipase D/metabolism
  • Pyrrolidinones/pharmacology
  • Signal Transduction
  • Thapsigargin/pharmacology
  • Type C Phospholipases/antagonists & inhibitors
  • Virulence Factors, Bordetella/pharmacology
Citation (ISO format)
NUSSE, Olivier et al. Store-operated Ca2+ influx and stimulation of exocytosis in HL-60 granulocytes. In: The Journal of biological chemistry, 1997, vol. 272, n° 45, p. 28360–28367. doi: 10.1074/jbc.272.45.28360
Updates (1)
ISSN of the journal0021-9258

Technical informations

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