title: Overlapping roles for endothelial selectins in murine hematopoietic stem/progenitor cell homing to bone marrow.
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.
authors.affiliation: Department of Microbiology-Immunology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA.
authors.forename: L Karina
authors.initials: LK
authors.lastname: Nabors
authors.forename: Leo D
authors.initials: LD
authors.lastname: Wang
authors.forename: Amy J
authors.initials: AJ
authors.lastname: Wagers
authors.forename: Geoffrey S
authors.initials: GS
authors.lastname: Kansas
mesh_terms: D000818:Animals; D016026:Bone Marrow Transplantation; D019070:Cell Lineage; D002465:Cell Movement; D019040:E-Selectin / Q000235:genetics / Q000502:physiology*; D004730:Endothelium, Vascular / Q000166:cytology; D005260:Female; D005786:Gene Expression Regulation; D006085:Graft Survival; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000378:metabolism; D018960:Hyaluronan Receptors / Q000096:biosynthesis / Q000235:genetics; D007239:Infections; D008024:Ligands; D008297:Male; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008954:Models, Biological; D019007:P-Selectin / Q000235:genetics / Q000502:physiology*; D011183:Postoperative Complications; D011828:Radiation Chimera
chemical_list: C476399:Cd44 protein, mouse; D019040:E-Selectin; D018960:Hyaluronan Receptors; D008024:Ligands; D008562:Membrane Glycoproteins; D019007:P-Selectin; C084882:P-selectin ligand protein