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

It has been shown that deletion of the chemokine receptor, CXCR4, causes di sordered angiogenesis in mouse models. In the present studies, we examined the distribution and trafficking of CXCR4 in human endothelial cells, teste d 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 viruse s. The results show that CXCR4 is present on endothelial cells from coronar y arteries, iliac arteries and umbilical veins (HUVEC), but expression was heterogeneous, with some cells expressing CXCR4 on their surface, while oth ers did not. Addition of SDF-1 caused a rapid decrease in CXCR4 surface exp ression. It also caused CXCR4-mediated activation of MAPK, release of PGI(2 ), endothelial migration, and the formation of capillary-like structures by endothelial cells in culture. Go-culture of HUVEC with lymphoid cells that were chronically infected with a CD4-independent/CXCR4-tropic variant of H IV-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 endoth elial cells; (2) the CXCR4 ligand, SDF-1, can evoke a wide variety of respo nses from human endothelial cells; and (3) CXCR4 on endothelial cells can s erve as a receptor for isolates of HIV that can utilize chemokine receptors in the absence of CD4. (C) 2000 Elsevier Science B.V. All rights reserved.