PSGL-1 is a functional E-selectin ligand on HPCs. Bone marrow nucleated cells were harvested from WT control mice and treated with either rat IgG or PS/2 and 4RA10 to block both α4 integrin and the segment of PSGL-1 that interacts with P-selectin. The homing activity remaining after PS/2 and 4RA10 treatment (shaded area) is mediated by E-selectin and its ligands. To evaluate the contribution of PSGL-1 as an E-selectin ligand, PSGL-1 ^–/– BMNCs were concomitantly transplanted into lethally irradiated WT recipients. Homing of PSGL-1^–/– HPCs was further reduced when α4 integrin was blocked, suggesting that PSGL-1 contributes to HPC homing as an E-selectin ligand (*P < .05, **P < .01). Lodgment of HPCs in spleen was significantly reduced when PSGL-1 was inhibited or absent (*P < .05, **P < .01 compared with rat IgG control group). n = 6 to 7 mice per group.