Transient elevations of cytosolic free calcium retard subsequent apoptosis in neutrophils in vitro

Moira K. B. Whyte, Simon J Hardwick, Laura C Meagher, John S Savill, Christopher Haslett

Research output: Contribution to journalArticlepeer-review

Abstract

Elevation of cytosolic calcium ([Ca2+]i) has been reported to induce apoptosis in a number of cell types. However, in the neutrophil, which undergoes apoptosis constitutively during aging in vitro, activation by inflammatory mediators elevates [Ca2+]i and prolongs lifespan via inhibition of apoptosis. To examine this paradox, we investigated the effects of modulation of [Ca2+]i upon apoptosis of neutrophils in vitro. Calcium ionophores (A23187, ionomycin) retarded apoptosis in neutrophil populations after 20 h (P < 0.001). Conversely, intracellular Ca(2+)-chelation, using bis-(o-aminophenoxy)-N,N,N'N'-tetraacetic acid (BAPTA) acetoxymethyl ester (AM) promoted apoptosis (P < 0.02). W-7 (an inhibitor of calmodulin) also promoted apoptosis (P < 0.05). Measurements of [Ca2+]i, using fura-2, showed (a) increased apoptosis in neutrophil populations was not associated with elevated [Ca2+]i, (b) neutrophils cultured with ionophore at concentrations inhibiting apoptosis exhibited transient (< 1 h) elevations of [Ca2+]i, to levels previously reported with receptor-mediated stimuli, and (c) BAPTA was able to prevent the elevation of [Ca2+]i and the inhibition of apoptosis produced by ionophore. Modulation of apoptosis occurred without alterations in intracellular pH. Thus, in the neutrophil, unlike lymphoid cells, elevation of [Ca2+]i exerts an inhibitory effect upon apoptosis. Furthermore, these data suggest that transient elevation of [Ca2+]i elicits signaling events leading to prolonged inhibition of apoptosis.
Original languageEnglish
Pages (from-to)446-55
Number of pages10
JournalJournal of Clinical Investigation
Volume92
Issue number1
DOIs
Publication statusPublished - Jul 1993

Keywords

  • APOPTOSIS
  • Calcimycin
  • CALMODULIN
  • Cytosol
  • Egtazic Acid
  • Endonucleases
  • HUMANS
  • HYDROGEN
  • Ionomycin
  • Neutrophils
  • SULFONAMIDES

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