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

Current understanding of the adhesion molecules and mechanisms regulating h ematopoietic stem and progenitor cell (HSPC) homing to the bone marrow is l imited. In contrast, the process by which mature leukocytes are able to hom e to and extravasate out of blood vessels at sites of inflammation has been well characterized and invites comparison. We studied the interaction of h uman HSPC from adult bone marrow (ABM) and fetal liver (FL) with E-, P-, an d 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 sh ear rates, indicating the presence of ligands for all three selectins on HS PC, Results indicate that CD34(+) ABM and FL cells roll more efficiently (t o a greater extent and more slowly) than more differentiated CD34(-) cells, especially on P- and L-selectin. In a similar fashion, increased rolling e fficiency was seen with CD34(+)CD38(-) ABM cells when compared with committ ed progenitor cells of the CD34(+)CD38(+) phenotype, Rolling of CD34(+) ABM cells on P-selectin could be partially inhibited by monoclonal antibody (m Ab) against PSGL-1, and was not inhibited by a mAb against CD34, suggesting that HSPC have unique carbohydrate repertoires that facilitate selectin-me diated rolling, Our results provide direct evidence of selectin ligands on HSPC under physiologic flow conditions and are the first to show a correlat ion between the maturity of HSPC during development and rolling efficiency on selectins, suggesting a mechanism by which HSPC subsets may differential ly home to the extravascular spaces of the bone marrow, (Blood. 2000;95:478 -486) (C) 2000 by The American Society of Hematology.