Chemokine Receptors in Human Endothelial Cells

• Published in: The Journal of biological chemistry Vol. 273; no. 7; pp. 4282 - 4287
• Main Authors: Gupta, Shalley K., Lysko, Paul G., Pillarisetti, Kodandaram, Ohlstein, Eliot, Stadel, Jeffrey M.
• Format: Journal Article
• Language: English
• Published: American Society for Biochemistry and Molecular Biology 01-02-1998
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.273.7.4282

Chemokines play an important role in the regulation of endothelial cell (EC) function, including proliferation, migration
and differentiation during angiogenesis, and re-endothelialization after injury. In this study, reverse transcriptase-polymerase
chain reaction was used to reveal expression of various CXC and CC chemokine receptors in human umbilical vein EC. Northern
analysis showed that CXCR4 was selectively expressed in vascular EC, but not in smooth muscle cells. Compared with other chemokines,
stromal cell-derived factor-1α (SDF-1α), the known CXCR4 ligand, was an efficacious chemoattractant for EC, causing the migration
of ∼40% input cells with an EC 50 of 10–20 n m . Of the chemokines tested, only SDF-1α induced a rapid, though variable mobilization of intracellular Ca 2+ in EC. Experiments with actinomycin D demonstrated that CXCR4 transcripts were short-lived, indicating a rapid mRNA turnover.
Interferon-γ (IFN-γ) caused a pronounced down-regulation of CXCR4 mRNA in a concentration- and time-dependent manner. In a
striking functional correlation, IFN-γ treatment also attenuated the chemotactic response of EC to SDF-1α. IL-1β, tumor necrosis
factor-α, and lipopolysaccharide produced a time course-dependent biphasic effect on CXCR4 transcription. Expression of CXCR4
in EC is significant, more so as it and several CC chemokine receptors have been shown to serve as fusion co-receptors along
with CD4 during human immunodeficiency virus infection. Taken together, these findings provide evidence of chemokine receptor
expression in EC and offer an explanation for the action of chemokines like SDF-1α on the vascular endothelium.