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

Interleukin-8 (IL-8) plays an important role in the activation of neutrophi l granulocytes. Although intracellular Ca2+ signals are essential in this p rocess, they have not been studied in great detail so far. Here, we have me asured IL-8-induced Ca2+ signals in single human neutrophil granulocytes us ing the Ca2+ indicator dye FURA-2 AM and we have investigated the signal tr ansduction that leads to these Ca2+ signals with various pharmacological to ols. Our results indicate that IL-8-induced Ca2+ signals consist of at leas t two components. An initial fast component was followed by a smaller and m ore persistent one. The initial Ca2+ signal was independent of extracellula r 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 ex tracellular Ca2+ was removed suggesting that it was generated by Ca2+ influ x through Ca2+ release-activated Ca2+ (CRAC) channels. This Ca2+ influx may prolong IL-8-induced Ca2+ signals during granulocyte activation.