Abstract：
: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-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 wild-type 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 alpha(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 an E-selectin ligand(s) other than PSGL-1 transduces growth inhibitory and proapoptotic signals and requires posttranslational fucosylation to be functional.
journal_name
Bloodjournal_title
Bloodauthors
Winkler IG,Snapp KR,Simmons PJ,Lévesque JPdoi
10.1182/blood-2003-06-1921subject
Has Abstractpub_date
2004-03-01 00:00:00pages
1685-92issue
5eissn
0006-4971issn
1528-0020pii
2003-06-1921journal_volume
103pub_type
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