on February 26, 2004
Published online before print February 26, 2004, doi: 10.1161/01.ATV.0000124102.11472.36
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Submitted on December 1, 2003
Accepted on February 4, 2004
CXCL16/SR-PSOX Is an Interferon-
-Regulated Chemokine and Scavenger Receptor Expressed in Atherosclerotic Lesions
Dirk M. Wuttge ;
From the Center for Molecular Medicine and the Department of Medicine (D.M.W., X.Z., Y.S., V.S., S.S., G.K.H., A.S.), the Department of Surgery (U.H.), and the Department of Surgery Science (S.S.), Karolinska Hospital, Karolinska Institute, Stockholm, Sweden; and Division of Biomedicine and the Department of Health Care Science (A.S., D.W.), University of Örebro, Sweden.
* To whom correspondence should be addressed. E-mail: allan.sirsjo{at}ivo.oru.se.
Objective--Atherosclerosis is an inflammatory disease. Several chemokines are important for monocyte/macrophage and T-cell recruitment to the lesion. CXCL16 is a recently discovered chemokine that is expressed in soluble and transmembrane forms, ligates CXCR6 chemokine receptor, and guides migration of activated Th1 and Tc1 cells. It is identical to scavenger receptor SR-PSOX, which mediates uptake of oxidized low-density lipoprotein. We investigated whether CXCL16 expression is controlled by interferon-
(IFN-) cytokine-abundant in atherosclerotic lesions.
Methods and Results--CXCL16 and CXCR6 expression was identified by polymerase chain reaction and histochemistry in atherosclerotic lesions from humans and apolipoprotein-E-deficient mice. In vitro IFN--induced CXCL16 in human monocytic THP-1 cells and primary human monocytes, which led to increased uptake of oxidized low-density lipoprotein in THP-1 cells, which could be blocked by peptide antibodies against CXCL16. In vivo IFN- induces CXCL16 expression in murine atherosclerotic lesions.
Conclusions--We demonstrate a novel role of IFN- in foam cell formation through upregulation of CXCL16/SR-PSOX. CXCR6 expression in the plaque confirms the presence of cells able to respond to CXCL16. Therefore, this chemokine/scavenger receptor could serve as a molecular link between lipid metabolism and immune activity in the atherosclerotic lesion.
Key words: atherosclerosis • chemokines • interferon-
•
oxidized low-density lipoprotein •
scavenger receptors
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