title: Store-operated Ca2+ influx and stimulation of exocytosis in HL-60 granulocytes.
abstract: 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.
authors.affiliation: Division of Infectious Diseases, University Hospital Geneva, 1211 Geneva 14, Switzerland. nuesse@dmivov1.hcuge.ch
authors.forename: O
authors.initials: O
authors.lastname: Nüsse
authors.forename: L
authors.initials: L
authors.lastname: Serrander
authors.forename: R
authors.initials: R
authors.lastname: Foyouzi-Youssefi
authors.forename: A
authors.initials: A
authors.lastname: Monod
authors.forename: D P
authors.initials: DP
authors.lastname: Lew
authors.forename: K H
authors.initials: KH
authors.lastname: Krause
mesh_terms: D000730:Androstadienes / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D003594:Cytoplasmic Granules / Q000187:drug effects / Q000378:metabolism; D004357:Drug Synergism; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004963:Estrenes / Q000494:pharmacology; D005089:Exocytosis / Q000187:drug effects; D019204:GTP-Binding Proteins / Q000378:metabolism; D019833:Genistein / Q000494:pharmacology; D006098:Granulocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D018922:HL-60 Cells; D006801:Humans; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D037342:Pertussis Toxin; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D010739:Phospholipase D / Q000378:metabolism; D011760:Pyrrolidinones / Q000494:pharmacology; D015398:Signal Transduction; D019284:Thapsigargin / Q000494:pharmacology; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors; D010566:Virulence Factors, Bordetella / Q000494:pharmacology; D000077191:Wortmannin
chemical_list: D000730:Androstadienes; D004791:Enzyme Inhibitors; D004963:Estrenes; D010726:Phosphodiesterase Inhibitors; D011760:Pyrrolidinones; D010566:Virulence Factors, Bordetella; C060229:1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione; D009240:N-Formylmethionine Leucyl-Phenylalanine; D019284:Thapsigargin; D019833:Genistein; D037342:Pertussis Toxin; D019869:Phosphatidylinositol 3-Kinases; D010738:Type C Phospholipases; D010739:Phospholipase D; D019204:GTP-Binding Proteins; D002118:Calcium; D000077191:Wortmannin