Proteoglycans guide SDF-1-induced migration of hematopoietic progenitor cells.
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.
Netelenbos
Tanja
T
Department of Hematology, Vrije Universiteit Medical Center, Amsterdam, The Netherlands.
Zuijderduijn
Suzanne
S
Van Den Born
Jacob
J
Kessler
Floortje L
FL
Zweegman
Sonja
S
Huijgens
Peter C
PC
Dräger
Angelika M
AM
D001853:Bone Marrow / Q000098:blood supply / Q000737:chemistry*; D002448:Cell Adhesion / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured / Q000187:drug effects; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000737:chemistry / Q000166:cytology; D005109:Extracellular Matrix / Q000737:chemistry; D005353:Fibronectins / Q000378:metabolism / Q000494:pharmacology; D018922:HL-60 Cells / Q000187:drug effects; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000187:drug effects*; D006493:Heparin / Q000737:chemistry / Q000494:pharmacology; D006497:Heparan Sulfate / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D046911:Macromolecular Substances; D009994:Osmolar Concentration; D011485:Protein Binding; D011509:Proteoglycans / Q000737:chemistry / Q000494:pharmacology* / Q000502:physiology; D019718:Receptors, CXCR4 / Q000187:drug effects / Q000378:metabolism; D012995:Solubility; D013329:Structure-Activity Relationship; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism / Q000494:pharmacology
D054377:Chemokine CXCL12; D019743:Chemokines, CXC; D005353:Fibronectins; D006493:Heparin; D006497:Heparan Sulfate; D046911:Macromolecular Substances; D011509:Proteoglycans; D019718:Receptors, CXCR4; D019010:Vascular Cell Adhesion Molecule-1; C515255:CXCL12 protein, human