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.
| Original language | English |
|---|---|
| Pages (from-to) | 353-362 |
| Number of pages | 10 |
| Journal | Journal of Leukocyte Biology |
| Volume | 72 |
| Issue number | 2 |
| DOIs | |
| Publication status | Published - Aug-2002 |
Keywords
- Bone Marrow/blood supply
- Cell Adhesion/drug effects
- Cell Movement/drug effects
- Cells, Cultured/drug effects
- Chemokine CXCL12
- Chemokines, CXC/administration & dosage
- Dose-Response Relationship, Drug
- Endothelium, Vascular/chemistry
- Extracellular Matrix/chemistry
- Fibronectins/metabolism
- HL-60 Cells/drug effects
- Hematopoietic Stem Cells/cytology
- Heparin/chemistry
- Heparitin Sulfate/chemistry
- Humans
- Macromolecular Substances
- Osmolar Concentration
- Protein Binding
- Proteoglycans/chemistry
- Receptors, CXCR4/drug effects
- Solubility
- Structure-Activity Relationship
- Vascular Cell Adhesion Molecule-1/metabolism