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Blood, 1 March 2004, Vol. 103, No. 5, pp. 1685-1692.
Prepublished online as a Blood First Edition Paper on October 30, 2003; DOI 10.1182/blood-2003-06-1921.

Submitted June 16, 2003
Accepted October 20, 2003
Adhesion to E-selectin promotes growth inhibition and apoptosis of human and murine hematopoietic progenitor cells independent of PSGL-1
Ingrid G Winkler*, Karen R Snapp, Paul J Simmons, and Jean-Pierre Levesque
Adhesive Interactions and Cell Trafficking Laboratory, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia; Stem Cell Biology Program, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia
Department of Pharmacology, College of Medicine, University of Illinois at Chicago, Chicago, IL, USA
* Corresponding author; email: ingrid.winkler{at}petermac.org.
Although both P- and E-selectin are constitutively expressed on bone marrow endothelial cells, their role in the regulation of hematopoiesis has only recently been investigated. We have previously shown that P-selectin glycoprotein ligand-l (PSGL-1/CD162) is expressed by primitive human bone marrow CD34+ cells, mediates their adhesion to P-selectin and more importantly, inhibits their proliferation. We now demonstrate that adhesion to E-selectin inhibits the proliferation of human CD34+ cells isolated either from human umbilical cord blood, adult mobilized blood or steady-state bone marrow. Furthermore a subpopulation, that does not contain the most primitive hematopoietic progenitor cells, undergoes apoptosis following E-selectin-mediated adhesion. The same phenomenon was observed in cells isolated from mouse bone marrow. Using lineage-negative Sca-1+ c-KIT+ bone marrow cells from PSGL-1-/- and wildtype mice, we establish that PSGL-1 is not the ligand involved in E-selectin-mediated growth inhibition and apoptosis. Moreover, stable transfection of the human myeloid cell line K562 (which does not express PSGL-1), with (1,3) fucosyltransferase VII alone was sufficient to recapitulate the E-selectin-mediated growth inhibition and apoptosis observed in hematopoietic progenitor cells. These data demonstrate that E-selectin ligand(s) other than PSGL-1 transduce growth inhibitory and pro-apoptotic signals and require post-translational fucosylation to be functional.

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