Working model of TNF-α- and FAS ligand–induced neutrophil apoptosis. Left panel shows that TNFR1 ligation results in p38 activation. p38 further activates the PI3K signaling pathway and ROS generation. ROS increase caspase-3 activity, leading to apoptosis. Right panel shows that ligation of FAS results in caspase-8 processing, which further activates caspase-3 and BID. BID cleavage launches the mitochondrial amplification loop, leading to mitochondrial outer membrane permeabilization, cytochrome c release, apoptosome formation, and caspase-3 activation, resulting in apoptosis.