Mechanisms of IL-8-induced Ca2+ signaling in human neutrophil granulocytes

Eur J Immunol. 1999 Mar;29(3):897-904. doi: 10.1002/(SICI)1521-4141(199903)29:03<897::AID-IMMU897>3.0.CO;2-5.

Abstract

Interleukin-8 (IL-8) plays an important role in the activation of neutrophil granulocytes. Although intracellular Ca2+ signals are essential in this process, they have not been studied in great detail so far. Here, we have measured IL-8-induced Ca2+ signals in single human neutrophil granulocytes using the Ca2+ indicator dye FURA-2 AM and we have investigated the signal transduction that leads to these Ca2+ signals with various pharmacological tools. Our results indicate that IL-8-induced Ca2+ signals consist of at least two components. An initial fast component was followed by a smaller and more persistent one. The initial Ca2+ signal was independent of extracellular Ca2+. It required the activation of phospholipase C via a pertussis toxin sensitive G-protein and was due to activation of IP3 receptor-coupled Ca2+ release channels. The late phase of the Ca2+ signal was suppressed when extracellular Ca2+ was removed suggesting that it was generated by Ca2+ influx through Ca2+ release-activated Ca2+ (CRAC) channels. This Ca2+ influx may prolong IL-8-induced Ca2+ signals during granulocyte activation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bordetella pertussis
  • Calcium / metabolism
  • Calcium Channels / drug effects
  • Calcium Channels / metabolism
  • Calcium Channels / physiology
  • Calcium Signaling / physiology*
  • Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone / pharmacology
  • Cells, Cultured
  • Enzyme Inhibitors / pharmacology
  • Humans
  • Interleukin-8 / metabolism*
  • Interleukin-8 / pharmacology
  • Ionophores / pharmacology
  • Neutrophils / cytology
  • Neutrophils / drug effects
  • Neutrophils / metabolism*
  • Pertussis Toxin
  • Recombinant Proteins / metabolism
  • Recombinant Proteins / pharmacology
  • Thapsigargin / pharmacology
  • Type C Phospholipases / antagonists & inhibitors
  • Virulence Factors, Bordetella / pharmacology

Substances

  • Calcium Channels
  • Enzyme Inhibitors
  • Interleukin-8
  • Ionophores
  • Recombinant Proteins
  • Virulence Factors, Bordetella
  • Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone
  • Thapsigargin
  • Pertussis Toxin
  • Type C Phospholipases
  • Calcium