Expression and cellular localization of the CC chemokines PARC and ELC in human atherosclerotic plaques

Local immune responses are thought to play an important role in the develop ment of atherosclerosis, Histological studies have shown that human atheros clerotic 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 lymphoc ytes: PARC (pulmonary and activation-regulated chemokine), ELC (EBI1-ligand chemokine), LARC (liver and activation-regulated chemokine), and SLC (seco ndary lymphoid-tissue chemokine), Using reverse transcriptase-polymerase ch ain reaction and in situ hybridization, we have found gene expression for P ARC and ELC but not for LARC or SLC in human atherosclerotic plaques. Immun ohistochemical staining of serial plaque sections with specific cell marker s revealed highly different expression patterns of PARC and ELC. PARC mRNA was restricted to CD68(+) macrophages (n = 14 of 18),whereas ELC mRNA was w idely expressed by macrophages and intimal smooth muscle cells (SMC) in nea rly 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), Ve ry low levels of ELC mRNA expression could also be detected in normal mamma ry 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 stimu lated with tumor necrosis factor-alpha and interferon-gamma but not in SMC stimulated with serum. Both PARC and ELC mRNA were expressed by monocyte-de rived macrophages but not monocytes. The expression patterns of PARC and EL C mRNA in human atherosclerotic lesions suggest a potential role for these two recently described CC chemokines in attracting T lymphocytes into ather osclerotic lesions.