Relationship between selectin-mediated rolling of hematopoietic stem and progenitor cells and progression in hematopoietic development

Abstract

Current understanding of the adhesion molecules and mechanisms regulating hematopoietic stem and progenitor cell (HSPC) homing to the bone marrow is limited. In contrast, the process by which mature leukocytes are able to home to and extravasate out of blood vessels at sites of inflammation has been well characterized and invites comparison. We studied the interaction of human HSPC from adult bone marrow (ABM) and fetal liver (FL) with E-, P-, and L-selectin immobilized in a flow chamber. CD34+ HSPC from both ABM and FL rolled avidly on E-, P-, and L-selectin across a range of physiologic shear rates, indicating the presence of ligands for all three selectins on HSPC. Results indicate that CD34+ ABM and FL cells roll more efficiently (to a greater extent and more slowly) than more differentiated CD34− cells, especially on P- and L-selectin. In a similar fashion, increased rolling efficiency was seen with CD34+CD38− ABM cells when compared with committed progenitor cells of the CD34+CD38+ phenotype. Rolling of CD34+ ABM cells on P-selectin could be partially inhibited by monoclonal antibody (mAb) against PSGL-1, and was not inhibited by a mAb against CD34, suggesting that HSPC have unique carbohydrate repertoires that facilitate selectin-mediated rolling. Our results provide direct evidence of selectin ligands on HSPC under physiologic flow conditions and are the first to show a correlation between the maturity of HSPC during development and rolling efficiency on selectins, suggesting a mechanism by which HSPC subsets may differentially home to the extravascular spaces of the bone marrow.