In vitro model for hematopoietic progenitor cell homing reveals endothelial heparan sulfate proteoglycans as direct adhesive ligands.
Proteoglycans (PGs) play a dominant role within the bone marrow (BM), but their role in homing of transplanted hematopoietic progenitor cells (HPC) is unknown. In this study, the role of heparan sulfate (HS) PGs on BM endothelium as adhesive structures was investigated. HPC (primary CD34+ cells and cell line KG-1a) were able to bind fractionated heparin, which could be competed by highly sulfated heparin/HS-glycosaminoglycans (GAGs). Under flow conditions, HPC adhered to immobilized heparin after rolling over E-selectin. Rolling of KG-1a on BM endothelial cell (EC) line 4LHBMEC was completely E selectin-dependent. Addition of heparin/HS-GAGs, endothelial treatment with chlorate, or anti-HS all partially inhibited firm adhesion. Moreover, enzymatic removal of endothelial HS-GAGs reduced initial adhesion. Finally, HPC-bound PGs isolated from 4LHBMEC, which was largely inhibited by enzymatic HS-degradation. In summary, we identified sulfated structures on BM endothelium, most likely HSPGs, as a novel class of glycoconjugates involved in the multistep homing cascade of HPC.
Netelenbos
Tanja
T
Department of Hematology, Vrije Universiteit Medical Center, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands.
van den Born
Jacob
J
Kessler
Floortje L
FL
Zweegman
Sonja
S
Huijgens
Peter C
PC
Drager
Angelika M
AM
D018952:Antigens, CD34 / Q000378:metabolism; D001854:Bone Marrow Cells / Q000166:cytology; D002448:Cell Adhesion; D017931:DNA Primers / Q000737:chemistry; D019040:E-Selectin / Q000378:metabolism; D004730:Endothelium, Vascular / Q000378:metabolism*; D005434:Flow Cytometry; D006412:Hematopoietic Stem Cells / Q000378:metabolism*; D019812:Heparan Sulfate Proteoglycans / Q000502:physiology*; D006493:Heparin / Q000378:metabolism; D006801:Humans; D019041:L-Selectin / Q000378:metabolism; D011485:Protein Binding; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
D018952:Antigens, CD34; D017931:DNA Primers; D019040:E-Selectin; D019812:Heparan Sulfate Proteoglycans; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; D019041:L-Selectin; D006493:Heparin