Important note: Information in this article was accurate in 2000. The state of the art may have changed since the publication date.
CXCR4 on human endothelial cells can serve as both a mediator of biological responses and as a receptor for HIV-2.
Biochim Biophys Acta. 2000 Feb 21;1500(2):227-40. Unique Identifier : AIDSLINE MED/20125614 Molino M; Woolkalis MJ; Prevost N; Pratico D; Barnathan ES; Taraboletti G; Haggarty BS; Hesselgesser J; Horuk R; Hoxie JA; Brass LF; Consorzio Mario Negri Sud, Santa Maria Imbaro, Italy.
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 PGI(2), 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.
Keywords: JOURNAL ARTICLE Anti-HIV Agents/PHARMACOLOGY Calcium Signaling/DRUG EFFECTS Capillaries/CYTOLOGY Cell Fusion/DRUG EFFECTS Chemokines, CXC/PHARMACOLOGY Chemotaxis/DRUG EFFECTS Collagen Coronary Vessels/CYTOLOGY Cytopathogenic Effect, Viral/DRUG EFFECTS Down-Regulation (Physiology) Drug Combinations Endothelium, Vascular/DRUG EFFECTS/*METABOLISM/VIROLOGY Epoprostenol/SECRETION Flow Cytometry Gene Expression Human HIV-2/*PHYSIOLOGY Iliac Artery/CYTOLOGY Immunoenzyme Techniques Laminin Microscopy, Fluorescence Morphogenesis/DRUG EFFECTS MAP Kinase Signaling System/DRUG EFFECTS Proteoglycans Receptor Cross-Talk Receptors, CXCR4/GENETICS/*PHYSIOLOGY Receptors, Thrombin/PHYSIOLOGY Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. Tetradecanoylphorbol Acetate/PHARMACOLOGY Umbilical Veins/CYTOLOGY
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Important note: Information in this article was accurate in 2000. The state of the art may have changed since the publication date.
