Abstract
Selectins are carbohydrate-binding adhesion molecules that are critically involved in leukocyte recognition of endothelium. The endothelial selectins have been implicated in homing of hematopoietic stem and progenitor cells (HSPCs) to the bone marrow (BM) during bone marrow transplant (BMT), but the precise roles of individual selectins in this process have never been defined. BMT of lethally irradiated mice lacking both endothelial selectins (E/P KO) with limiting numbers of wild type BM cells rescued significantly fewer E/P KO than WT recipients, but higher numbers of transplanted WT cells rescued E/P KOs in a dose-dependent fashion. Short-term homing assays confirmed a substantial defect in HSPC homing to BM in E/P KO mice. In contrast, BMT of E-selectin null or P-selectin null mice at limiting cell number uniformly rescued greater than 95% of the transplanted animals. Consistent with these functional results, flow cytometric analysis revealed both E-selectin ligands and P-selectin ligands on distinct subsets of HSPC. These results demonstrate overlapping functions for the endothelial selectins in HSPC homing to BM in the setting of BMT, and define a novel aspect of HSPC heterogeneity linked to selectin ligand expression.
Original language | English (US) |
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Pages (from-to) | 588-596 |
Number of pages | 9 |
Journal | Experimental Hematology |
Volume | 41 |
Issue number | 7 |
DOIs | |
State | Published - Jul 2013 |
Funding
A.J.W. is an Early Career Scientist of the Howard Hughes Medical Institute. L.D.W. is a Damon Runyon-Sohn Foundation Fellow supported by the Damon Runyon Cancer Research Foundation (DRSG 2-12) and the St. Baldrick's Foundation. This work was supported by NIH grants HL058710 to GSK, 1RO1 HL088582 , and DP2 OD004345 (to A.J.W.) and 5T32 HL007574 (to L.D.W.).
ASJC Scopus subject areas
- Genetics
- Molecular Biology
- Hematology
- Cancer Research
- Cell Biology