The majority of neutrophil activating receptors induce

The majority of neutrophil-activating receptors induce extracellular calcium entry as an early signaling response to activate Carfilzomib functions, including phagocytosis, degranulation, and chemotaxis [108]. These membrane receptors induce generation of inositol 1,4,5-trisphosphate (IP3) which activates IP3Rs and Ca2+ release from the intracellular stores which is important for phagocytosis [137]. Depleted stores are reloaded by the sarco/endoplasmic reticulum Ca2+ ATPase SERCA, whereby calcium influx into the cell is enhanced through store-operated calcium channels [23]. This Ca2+ influx is also required for neutrophil ROS generation by stimulating Ca2+-dependent recruitment of S100A8/A9 proteins which act as Ca2+ sensors and can interact with flavocytochrome b558 and p67phox to promote ROS generation [25]. Moreover, Hv1 voltage-gated proton channels have been shown to extrude the protons and compensate the charge generated by NADPH oxidases, thereby enhancing the driving force for extracellular Ca2+ entry and sustaining NADPH oxidase activity [46].