Adhesion to E-selectin promotes growth inhibition and apoptosis of human and murine hematopoietic progenitor cells independent of PSGL-1.
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.
Adhesive Interactions and Cell Trafficking Laboratory, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia. ingrid.winkler@petermac.org
Ingrid G
IG
Winkler
Karen R
KR
Snapp
Paul J
PJ
Simmons
Jean-Pierre
JP
Lévesque
D000818:Animals; D018952:Antigens, CD34 / Q000096:biosynthesis; D017209:Apoptosis; D002448:Cell Adhesion; D002455:Cell Division; D019070:Cell Lineage; D019040:E-Selectin / Q000235:genetics* / Q000378:metabolism; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D006801:Humans; D020287:In Situ Nick-End Labeling; D020014:K562 Cells; D008024:Ligands; D008562:Membrane Glycoproteins / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D011401:Promoter Regions, Genetic; D011485:Protein Binding
D018952:Antigens, CD34; D019040:E-Selectin; D008024:Ligands; D008562:Membrane Glycoproteins; C084882:P-selectin ligand protein