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Proteoglycans on bone marrow endothelial cells bind and present SDF-1 towards hematopoietic progenitor cells

Leukemia volume 17, pages 175–184 (2003)Cite this article

Abstract

Recognition events between hematopoietic progenitor cells (HPC) and bone marrow endothelial cells (BMEC) initiate homing of HPC to the bone marrow. The chemokine SDF-1 is present on BMEC and plays a crucial role in bone marrow engraftment. We studied the role of proteoglycans (PGs) on BMEC in binding and presentation of SDF-1. SDF-1 mRNA was present in three human BMEC cell lines. Competition experiments showed that 125I-SDF-1α binding to the BMEC cell line 4LHBMEC was inhibited by heparins, heparan sulfate (HS) intestinal mucosa, chondroitin and dermatan sulfate (CS/DS), but not by HS bovine kidney. Pretreatment of 4LHBMEC with glycosaminoglycan (GAG)-degrading enzymes or sodium chlorate demonstrated that SDF-1 bound to both HSPGs and CS/DSPGs in a sulfation-dependent manner, as determined with an SDF-1 antibody recognizing the CXCR4-binding site. 4LHBMEC bound four-fold more SDF-1 than HUVEC. Isolated endothelial PGs did not bind SDF-1 in a filter or microplate-binding assay, suggesting the necessity of membrane association. In flow adhesion experiments, endothelial arrest of CXCR4+ KG-1 and not of CXCR4− KG-1a cells increased significantly when SDF-1 was presented on 4LHBMEC. In conclusion, SDF-1 is produced by BMEC and binds to the BMEC cell surface via HS and CS/DS-GAGs, thereby presenting its CXCR4 binding site to HPC contributing to their arrest.

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Acknowledgements

The anti-SDF-1α antibody K15C was a generous gift from F Arenzana-Seisdedos (Unité d'Immunologie Virale, Paris, France). The authors thank Jan van der Linden (Department of Pulmonary Diseases, Utrecht Medical Center, Utrecht, The Netherlands) for providing us with the Optimas 6.1 software and Suzanne Zuijderduijn for performing transmigration experiments.

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Authors and Affiliations

  1. Department of Hematology, Vrije Universiteit Medical Center, Amsterdam, The Netherlands

    T Netelenbos, F L Kessler, S Zweegman, P A Merle, J W van Oostveen, P C Huijgens & A M Dräger

  2. Department of Molecular Cell Biology, Vrije Universiteit Medical Center, Amsterdam, The Netherlands

    J van den Born

  3. CLB, Sanquin Blood Supply Foundation, and Laboratory for Experimental and Clinical Immunology, Amsterdam, The Netherlands

    J J Zwaginga

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  1. T Netelenbos
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Netelenbos, T., van den Born, J., Kessler, F. et al. Proteoglycans on bone marrow endothelial cells bind and present SDF-1 towards hematopoietic progenitor cells. Leukemia 17, 175–184 (2003). https://doi.org/10.1038/sj.leu.2402738

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