PSGL-1-dependent myeloid leukocyte activation

Cell-cell interactions mediating leukocyte recruitment and inflammation are crucial for host defense. Leukocyte recruitment into injured tissue proceeds in a multistep process. The first contact of leukocytes with endothelial cells ("capturing" or "tethering") is mediated by selectins and their counter-receptor P-selectin glyco-protein ligand (PSGL)-1. During capture and rolling, leukocytes collect different inflammatory signals, which can activate various pathways. Integration of these signals leads to leukocyte activation, integrin-mediated arrest, cytoskeleton rearrangement, polarization, and transmigration. PSGL-1 on leukocytes also binds to activated platelets, where P-selectin is expressed at locally high site densities following alpha-granule fusion with the plasma membrane. Here, we review the signaling functions of PSGL-1 and speculate how the different known signaling events might relate to different phases of leukocyte recruitment.