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Blood, Vol. 95 No. 2 (January 15), 2000:
pp. 478-486
Relationship between selectin-mediated rolling of hematopoietic
stem and progenitor cells and progression in hematopoietic development
Adam W. Greenberg,
William G. Kerr, and
Daniel A. Hammer
From the Department of Bioengineering and the Department of
Molecular and Cellular Engineering, Institute for Human Gene Therapy,
and the Department of Chemical Engineering, Institute for Medicine and
Engineering, University of Pennsylvania, Philadelphia, PA.
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.
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