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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.
HEMATOPOIESIS Adhesion to E-selectin promotes growth inhibition and apoptosis of human and murine hematopoietic progenitor cells independent of PSGL-1From the Adhesive Interactions and Cell Trafficking Laboratory, Stem Cell Biology Program, Peter MacCallum Cancer Centre, Melbourne,Australia; and the Department of Pharmacology College of Medicine, University of Illinois at Chicago, Chicago, IL.
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, which does not contain the most primitive hematopoietic progenitor cells, undergoes apoptosis following E-selectinmediated 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 wild-type mice, we establish that PSGL-1 is not the ligand involved in E-selectinmediated growth inhibition and apoptosis. Moreover, stable transfection of the human myeloid cell line K562 (which does not express PSGL-1) with
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