Working model of the role of PDI in the function of the β₂-integrin Mac-1 on neutrophils. The neutrophil β₂-integrin Mac-1 is shown in different activation states. The nonactivated state on the left side contains free thiols. Agonist-induced stimulation induces cytoplasmic events leading to inside-out signaling and the interaction of Mac-1 with its ligands. Mac-1 is modified by PDI. During neutrophil activation, sulfhydryls are generated in the α_M subunit of Mac-1, leading to Mac-1 clustering. S, sulfur; SH, thiol.