Schematic representation of the apoptotic pathways in neutrophils. Caspase-8 is activated after death receptor clustering and consequently activates Bid. Bid activates Bax, which multimerizes in the mitochondrial membrane, forming the permeability transition pore, through which Smac and cytochrome c are released. Smac competes with caspase-3 and -9 for binding with XIAP, thus removing its inhibitory effect from these caspases. Cytochrome c activates caspase-9 through the apoptosome. Finally, caspase-9 activates caspase-3, which executes the process of apoptosis. In parallel, Ca²⁺ levels rise spontaneously, which leads to the activation of calpains. The calpains cleave XIAP, resulting in a more rapid activation of caspases-9 and -3. G-CSF inhibits this rise in Ca²⁺, leading to inhibition of calpain activation, preventing the subsequent degradation of XIAP and causing a delay in the activation of caspases-9 and -3.