PSGL-1-mediated adhesion of human hematopoietic progenitors to P-selectin results in suppression of hematopoiesis

Cellular interactions are critical for the regulation of hematopoiesis. The sialomucin PSGL-1/CD162 mediates the attachment of mature leukocytes to P- selectin. We now show that PSGL-1 also functions as the sole receptor for P -selectin on primitive human CD34(+) hematopoietic progenitor cells (HPC). More importantly, ligation of PSGL-1 by immobilized or soluble ligand or an ti-PSGL-1 antibody results in a profound suppression of HPC proliferation s timulated by potent combinations of early acting hematopoietic growth facto rs. These data demonstrate an unanticipated but extremely marked growth-inh ibitory effect of P-selectin on hematopoiesis and provide direct evidence t hat PSGL-1, in addition to its well-documented role as an adhesion molecule on mature leukocytes, is a potent negative regulator of human hematopoieti c progenitors.