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From the Department of Vascular Biology,*
SmithKline
Beecham Pharmaceuticals, New Frontiers Science Park North, Coldharbour
Road, Harlow, Essex, the United Kingdom, Department of Pulmonary
Pharmacology,
SmithKline Beecham
Pharmaceuticals, King of Prussia, Pennsylvania, and Department of
Surgery,
St. Thomas's Hospital, London,
the United Kingdom
Local immune responses are thought to play an important role in the
development of atherosclerosis. Histological studies have shown that
human atherosclerotic lesions contain T lymphocytes throughout all
stages of development, many of which are in an activated state.
A number of novel CC chemokines have been described recently,
which are potent chemoattractants for lymphocytes: PARC (pulmonary and
activation-regulated chemokine), ELC (EBI1-ligand
chemokine), LARC (liver and activation-regulated
chemokine), and SLC (secondary lymphoid-tissue chemokine).
Using reverse transcriptase-polymerase chain reaction and in
situ hybridization, we have found gene expression for
PARC and ELC but not for LARC or SLC in human atherosclerotic plaques.
Immunohistochemical staining of serial plaque sections with specific
cell markers revealed highly different expression patterns of PARC and
ELC. PARC mRNA was restricted to CD68+ macrophages
(n = 14 of 18), whereas ELC mRNA was widely
expressed by macrophages and intimal smooth muscle cells (SMC) in
nearly all of the lesions examined (n = 12 of 14). ELC
mRNA was also found to be expressed in the medial SMC wall of highly
calcified plaques (n = 4). Very low levels of ELC mRNA
expression could also be detected in normal mammary arteries but no
mRNA expression for PARC was detected in these vessels
(n = 4). In vitro, ELC mRNA was
found to be up-regulated in aortic SMC stimulated with tumor necrosis
factor-
and interferon-
but not in SMC stimulated with serum.
Both PARC and ELC mRNA were expressed by monocyte-derived macrophages
but not monocytes. The expression patterns of PARC and ELC mRNA in
human atherosclerotic lesions suggest a potential role for these two
recently described CC chemokines in attracting T lymphocytes into
atherosclerotic lesions.
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