CXCR4 on human endothelial cells can serve as both a mediator of biological responses and as a receptor for HIV-2

Marina Molino, Marilyn J. Woolkalis, Nicolas Prevost, Domenico Praticó, Elliot S. Barnathan, Giulia Taraboletti, Beth Stobenau Haggarty, Joseph Hesselgesser, Richard Horuk, James A. Hoxie, Lawrence F. Brass

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Abstract

It has been shown that deletion of the chemokine receptor, CXCR4, causes disordered angiogenesis in mouse models. In the present studies, we examined the distribution and trafficking of CXCR4 in human endothelial cells, tested their responses to the CXCR4 ligand, SDF-1, and asked whether endothelial cell CXCR4 can serve as a cell surface receptor for the binding of viruses. The results show that CXCR4 is present on endothelial cells from coronary arteries, iliac arteries and umbilical veins (HUVEC), but expression was heterogeneous, with some cells expressing CXCR4 on their surface, while others did not. Addition of SDF-1 caused a rapid decrease in CXCR4 surface expression. It also caused CXCR4-mediated activation of MAPK, release of PGI2, endothelial migration, and the formation of capillary-like structures by endothelial cells in culture. Co-culture of HUVEC with lymphoid cells that were chronically infected with a CD4-independent/CXCR4-tropic variant of HIV-2 resulted in the formation of multinucleated syncytia. Formation of the syncytia was inhibited by each of several different CXCR4 antibodies. Thus, our findings indicate: (1) that CXCR4 is widely expressed on human endothelial cells; (2) the CXCR4 ligand, SDF-1, can evoke a wide variety of responses from human endothelial cells; and (3) CXCR4 on endothelial cells can serve as a receptor for isolates of HIV that can utilize chemokine receptors in the absence of CD4. Copyright (C) 2000 Elsevier Science B.V.

Original languageEnglish
Pages (from-to)227-240
Number of pages14
JournalBiochimica et Biophysica Acta - Molecular Basis of Disease
Volume1500
Issue number2
DOIs
Publication statusPublished - Feb 21 2000

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Keywords

  • Chemokine
  • Chemokine receptor
  • CXCR4
  • Endothelial cell
  • HIV-2
  • SDF-1

ASJC Scopus subject areas

  • Molecular Biology
  • Molecular Medicine
  • Biophysics

Cite this

Molino, M., Woolkalis, M. J., Prevost, N., Praticó, D., Barnathan, E. S., Taraboletti, G., Haggarty, B. S., Hesselgesser, J., Horuk, R., Hoxie, J. A., & Brass, L. F. (2000). CXCR4 on human endothelial cells can serve as both a mediator of biological responses and as a receptor for HIV-2. Biochimica et Biophysica Acta - Molecular Basis of Disease, 1500(2), 227-240. https://doi.org/10.1016/S0925-4439(99)00110-6