CD44 is a major E-selectin ligand on human hematopoietic progenitor cells

E-selectin plays a critical role in mediating tissue-specific homing of T c ells into skin, and of primitive hematopoietic progenitor cells (HPCs) into bone marrow (BM). Though it is known that a glycoform of PSGL-1 (CLA) func tions as the principal E-selectin ligand on human T lymphocytes, the E-sele ctin Ligand(s) of human HPCs has not been identified. We used a shear-based adherence assay to analyze and define the E-selectin ligand activity of me mbrane proteins from human HPCs, Our data show that PSGL-1 expressed on hum an HPCs is an E-selectin ligand, and that HPCs also express a previously un recognized E-selectin ligand, CD44, The E-selectin ligand activity of CD44 is conferred by the elaboration of sialylated, fucosylated binding determin ants on N-glycans. This glycoform of CD44 is expressed on primitive CD34+ h uman HPCs, but not on more mature hematopoietic cells. Under physiologic fl ow conditions, this molecule mediates E-selectin-dependent rolling interact ions over a wider shear range than that of PSGL-1, and promotes human HPC r olling interactions on E-selectin expressed on human BM endothelial cells. These findings offer new insights into the structural biology and physiolog y of CD44, and into the molecular basis of E-selectin-dependent adhesive in teractions that direct homing of human HPC to BM.