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J Biol Chem, Vol. 273, Issue 7, 4282-4287, February 13, 1998
From the Department of Cardiovascular Pharmacology, SmithKline
Beecham Pharmaceuticals, King of Prussia, Pennsylvania 19406
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-1
Chemokine Receptors in Human Endothelial Cells
FUNCTIONAL EXPRESSION OF CXCR4 AND ITS TRANSCRIPTIONAL
REGULATION BY INFLAMMATORY CYTOKINES
(SDF-1), the known
CXCR4 ligand, was an efficacious chemoattractant for EC, causing the
migration of ~40% input cells with an EC50 of
10-20 nM. Of the chemokines tested, only SDF-1 induced
a rapid, though variable mobilization of intracellular Ca2+
in EC. Experiments with actinomycin D demonstrated that CXCR4 transcripts were short-lived, indicating a rapid mRNA turnover. Interferon-
(IFN-) caused a pronounced down-regulation of CXCR4 mRNA in a concentration- and time-dependent manner. In
a striking functional correlation, IFN- treatment also attenuated
the chemotactic response of EC to SDF-1. IL-1
, tumor necrosis
factor-, 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-1 on the vascular endothelium.
Copyright © 1998 by The American Society for Biochemistry and Molecular Biology, Inc.
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