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.

Characterization of a Lineage‐Negative Stem‐Progenitor Cell Population Optimized for Ex Vivo Expansion and Enriched for LTC‐IC

“…Furthermore, Lincells were highly positive for CXCR4 (>48%, the stromal-derived factor-1 receptor) and CD162 (>96%, also known as P-selectin glycoprotein ligand-1). Both molecules were previously reported as essential for HSPC homing and adhesion when repopulating/developing in the BM [24][25][26][27]42]. High expression levels of these markers may also correlate with the circulatory nature of UCB cells.…”

“…The Lincell subset was negative for a wide range of hematopoietic lineage markers, including CD45, glycophorin-A, CD38, CD7, CD33, CD56, CD16, CD3, and CD2. A proportion of Lin -HSPC nonetheless expressed markers: A) reflecting their immaturity status [21][22][23], such as CD133 (7.0% ± 0.8%), CD34 (14.4% ± 3.6%), intracellular CD34 (16.2% ± 0.6%), and CD164 (16.0% ± 4.1%), or B) that were involved in HSPC migration, adhesion, and homing to the bone marrow (BM) [24][25][26][27], CXCR4 (48.6% ± 4.0%), and CD162 (96.7% ± 2.0%) ( Fig. 1).…”

Synergy between proinflammatory ligands of G protein-coupled receptors in neutrophil activation and migration

“…One representative experiment is shown out of four independent experiments. that support migration across the bone marrow endothelium [43,44]. Conversely, the CXC chemokines CTAP-III and NAP-2 did not synergize with IL-8 in neutrophil chemotaxis.…”

Investigating the Feasibility of Stem Cell Enrichment Mediated by Immobilized Selectins

“…CD34+ HSPCs isolated using immunomagnetic cell enrichment methods have exhibited lower rolling velocities and higher rolling fluxes on immobilized E-, L-, and P-selectin than more differentiated CD34-hematopoietic cells (16,17). Rolling is a typical event in leukocyte recruitment to sites of inflammation, as well as lymphocyte and stem cell homing, and is mediated by transient interactions between selectins and their ligands, in the presence of calcium ion (18,19).…”