Mechanisms of IL-8-induced Ca2+ signaling in human neutrophil granulocytes.
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.
Schorr
W
W
Institut für Experimentelle und Klinische Pharmakologie und Toxikologie, Universität Erlangen-Nürnberg, Erlangen, Germany.
Swandulla
D
D
Zeilhofer
H U
HU
D001886:Bordetella pertussis; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D020013:Calcium Signaling / Q000502:physiology*; D002259:Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone / Q000494:pharmacology; D002478:Cells, Cultured; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism* / Q000494:pharmacology; D007476:Ionophores / Q000494:pharmacology; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D037342:Pertussis Toxin; D011994:Recombinant Proteins / Q000378:metabolism / Q000494:pharmacology; D019284:Thapsigargin / Q000494:pharmacology; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D015220:Calcium Channels; D004791:Enzyme Inhibitors; D016209:Interleukin-8; D007476:Ionophores; D011994:Recombinant Proteins; D010566:Virulence Factors, Bordetella; D002259:Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone; D019284:Thapsigargin; D037342:Pertussis Toxin; D010738:Type C Phospholipases; D002118:Calcium