Glycobiology Advance Access published online on March 19, 2004
Glycobiology, doi:10.1093/glycob/cwh038
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© 2004 Glycobiology © Oxford University Press 2004; all rights reserved.
ORIGINAL ARTICLES
1 Laboratoire de Biologie Cellulaire, Biothérapies Bénéfices et Risques, UPRES 3410, and Hôpital Jean Verdier, 93, Bondy, France The Stromal cell-Derived Factor-1 (SDF-1) is a CXC chemokine, which plays critical roles in migration, proliferation and differenciation of leukocytes. SDF-1 is the only known ligand of CXCR4, the co-receptor of X4 HIV strains. We show that SDF-1 binds to high and low affinity sites on HeLa cells. Co-immunoprecipitation studies demonstrate that glycanated and oligomerized syndecan-4, but neither syndecan-1, syndecan-2, betaglycan nor CD44 forms complexes with SDF-1 and CXCR4 on these cells as well as on primary lymphocytes or macrophages. Moreover, biotinylated SDF-1 directly binds in a glycosaminoglycans (GAGs)-dependent manner to electroblotted syndecan-4 and colocalization of SDF-1 with syndecan-4 was visualized by confocal microscopy. Glycosaminidases pre-treatment of the HeLa cells or the macrophages decreases the binding of syndecan-4 to the complex formed by SDF-1 and syndecan-4. In addition, this treatment also decreases the binding of the chemokine to CXCR4 on the primary macrophages, but not on the HeLa cells. Therefore, GAGs-dependent binding of SDF-1 to the cells facilitates SDF-1 binding to CXCR4 on primary macrophages but not on HeLa cell line. Finally, a SDF-1 independent heteromeric complex between syndecan-4 and CXCR4 was visualized on HeLa cells by confocal microscopy as well as by electron microscopy. Moreover, syndecan-4 from lymphocytes, monocyte derived-macrophages and HeLa cells co-immunoprecipitated with CXCR4. This syndecan-4/CXCR4 complex is likely a functional unit which is involved in SDF-1 binding. The role of these interactions in the pathophysiology of SDF-1 deserves further study.
Revised on October 21, 2003
Accepted on November 21, 2003
A syndecan-4/CXCR4 complex expressed on human primary lymphocytes and macrophages, and HeLa cell line binds the CXC chemokine, stromal cell derived factor-1 (SDF-1)
2 Laboratoire de Ciblage Fonctionnel des Tumeurs Solides, UPRES 2360, UFR-SMBH, Université Paris XIII, 74, rue Marcel Cachin, 93017, Bobigny, France
SDF-1, CXCR4, Syndecans, HIV
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