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

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.