Abstract
Stromal cell-derived factor-1 (SDF-1) is a chemoattractant involved in hematopoietic progenitor cell (HPC) trafficking to the bone marrow. We studied the role of bone marrow endothelial proteoglycans (PGs) in SDF-1-mediated migration of HPC using a transwell assay. A subclone of progenitor cell line KG-1 (KG-1v) was used, displaying CXCR4-dependent transmigration. Cell surface PGs on bone marrow endothelial cell line 4LHBMEC did not mediate SDF-1-induced transendothelial migration. In contrast, transwell filters precoated with various glycosaminoglycans (GAGs) enhanced migration toward SDF-1. SDF-1-induced migration was reduced by degradation of heparan sulfate in subendothelial matrix produced by 4LHBMEC. The stimulating effect of GAGs was caused by the formation of a stable haptotactic SDF-1 gradient, as SDF-1 bound to immobilized GAGs and triggered migration. Soluble heparan sulfate enhanced SDF-1-induced migration dose-dependently, suggesting that SDF-1-heparan sulfate complexes optimized SDF-1 presentation. In conclusion, we provide evidence that PGs in the subendothelial matrix establish an SDF-1 gradient guiding migrating HPC into the bone marrow.
MeSH terms
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Bone Marrow / blood supply
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Bone Marrow / chemistry*
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Cell Adhesion / drug effects
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Cell Movement / drug effects
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Cells, Cultured / drug effects
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Chemokine CXCL12
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Chemokines, CXC / administration & dosage
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Chemokines, CXC / chemistry
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Chemokines, CXC / pharmacology*
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Dose-Response Relationship, Drug
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Endothelium, Vascular / chemistry
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Endothelium, Vascular / cytology
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Extracellular Matrix / chemistry
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Fibronectins / metabolism
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Fibronectins / pharmacology
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HL-60 Cells / drug effects
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Hematopoietic Stem Cells / cytology
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Hematopoietic Stem Cells / drug effects*
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Heparin / chemistry
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Heparin / pharmacology
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Heparitin Sulfate / chemistry
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Heparitin Sulfate / pharmacology
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Humans
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Macromolecular Substances
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Osmolar Concentration
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Protein Binding
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Proteoglycans / chemistry
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Proteoglycans / pharmacology*
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Proteoglycans / physiology
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Receptors, CXCR4 / drug effects
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Receptors, CXCR4 / metabolism
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Solubility
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Structure-Activity Relationship
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Vascular Cell Adhesion Molecule-1 / metabolism
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Vascular Cell Adhesion Molecule-1 / pharmacology
Substances
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CXCL12 protein, human
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Chemokine CXCL12
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Chemokines, CXC
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Fibronectins
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Macromolecular Substances
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Proteoglycans
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Receptors, CXCR4
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Vascular Cell Adhesion Molecule-1
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Heparin
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Heparitin Sulfate