Expression of the Novel Scavenger Receptor SR-PSOX in Cultured Aortic Smooth Muscle Cells and Umbilical Endothelial Cells

Hofnagel, Oliver; Luechtenborg, Birgit; Plenz, Gabriele; Robenek, Horst

doi:10.1161/01.atv.0000012402.85056.45

Cited by 60 publications

(31 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Previous studies demonstrated the expression of CXCL16 on dendritic cells, macrophages, T cells, B cells, smooth muscle cells, and umbilical endothelial cells (4,5,(9)(10)(11). FLS from patients with RA are additional and new members of the group of cells producing CXCL16.…”

Section: Discussionmentioning

confidence: 97%

Pathogenic role of the CXCL16–CXCR6 pathway in rheumatoid arthritis

Nanki¹,

Shimaoka²,

Hayashida³

et al. 2005

Arthritis & Rheumatism

135

114

View full text Add to dashboard Cite

Objective. Rheumatoid arthritis (RA) is a chronic inflammatory disease associated with massive T cell infiltration into the synovium. The accumulated T cells express type 1 cytokines, such as interferon-␥ (IFN␥) and tumor necrosis factor ␣, and activated markers of inflammation, such as CD154 and inducible costimulator (ICOS). It is thought that chemokines contribute to T cell accumulation in the synovium. In this study, we examined the role of CXCL16 and CXCR6 in T cell migration and stimulation in RA synovium.Methods. Expression of CXCL16 and CXCR6 was analyzed by immunohistochemistry, reverse transcription-polymerase chain reaction, Western blotting, and/or flow cytometry. Migration activity was assessed using a chemotaxis chamber. IFN␥ production was analyzed by enzyme-linked immunosorbent assay. The effect of anti-CXCL16 monoclonal antibody on murine collagen-induced arthritis (CIA) was evaluated.Results. CXCL16 was expressed in RA synovium.

show abstract

Section: Discussionmentioning

confidence: 97%

Pathogenic role of the CXCL16–CXCR6 pathway in rheumatoid arthritis

Nanki¹,

Shimaoka²,

Hayashida³

et al. 2005

Arthritis & Rheumatism

135

114

View full text Add to dashboard Cite

show abstract

“…18 CXCL16 is the only known ligand for CXCR6 and is expressed by dendritic cells, 16 macrophages, 19 T cells, 20 and cytokine-stimulated smooth muscle and endothelial cells. 21,22 The disintegrin and metalloproteinase ADAM10 is involved in CXCL16 cleavage from the cell membrane, 21 leading to the release of a soluble protein that functions as a chemoattractant for responsive leukocytes.…”

Section: Clinical Perspective P 1811mentioning

confidence: 99%

CXCR6 Promotes Atherosclerosis by Supporting T-Cell Homing, Interferon-γ Production, and Macrophage Accumulation in the Aortic Wall

et al. 2007

View full text Add to dashboard Cite

Background-T lymphocytes are thought to be important in atherosclerosis, but very little is known about the mechanisms of lymphocyte recruitment into atherosclerosis-prone aortas. In this study we tested the hypothesis that CXCR6, a chemokine receptor that is expressed on a subset of CD4 ϩ T helper 1 cells and natural killer T cells, is involved in lymphocyte homing into the aortic wall and modulates the development and progression of atherosclerosis. Methods and Results-To investigate the role of CXCR6 in the development and progression of atherosclerosis, we bred CXCR6-deficient (CXCR6 GFP/GFP ) mice with apolipoprotein E-deficient (ApoE Ϫ/Ϫ ) mice. We found that CXCR6 Key Words: atherosclerosis Ⅲ immune system Ⅲ leukocytes Ⅲ lymphocytes Ⅲ vessels A therosclerotic lesions are characterized by lipid accumulation, cell death, fibrosis, and chronic vascular inflammation. 1 The body of evidence is growing that T and B lymphocytes, dendritic cells, and macrophages reside within the noninflamed aortic wall, and a significant influx of macrophages and T cells correlates with the development and progression of atherosclerosis. [2][3][4] The molecular mechanisms, kinetics of trafficking, and retention of different types of immune cells within the noninflamed and atherosclerosisprone aortic wall are not well defined. Most of the focus to date has been on the ability of monocytes to migrate to the atherosclerotic wall. 5 P-selectin, vascular cell adhesion molecule-1 (VCAM-1), P-selectin glycoprotein ligand-1 (PSGL-1), and ␣ 4 ␤ 1 integrin (VLA-4) are all involved in monocyte recruitment into atherosclerotic plaques, 6 and the chemokines CCL5 (regulated on activation, normal T cell expressed and secreted [RANTES]) and CXCL1 (keratinocyte-derived chemokine [KC]) are responsible for triggering monocyte adhesion on the atherosclerotic endothelium. [7][8][9] Lymphocyte trafficking into normal and atherosclerotic aortas is partially L-selectin dependent, 2 but little is known about other potential molecular mechanisms of lymphocyte recruitment. Clinical Perspective p 1811CXCR6 is a chemokine receptor expressed on some T helper 1 (Th1) and natural killer T (NKT) cells found in rheumatoid joints and inflamed livers. 10 CXCR6, also known as Bonzo/STRL33/TYMSTR, 11 is expressed on subpopulations of CD4 ϩ effector memory T cells, 10 on V␣ 24 ϩ NKT cells, 12,13 a Forkhead Box P3 The disintegrin and metalloproteinase ADAM10 is involved in CXCL16 cleavage from the cell membrane, 21 leading to the release of a soluble protein that functions as a chemoattractant for responsive leukocytes.In addition to its properties as a chemokine, CXCL16 acts also as a scavenger receptor for apoptotic cells, phosphatidylserine, and oxidized low-density lipoprotein. 16,19 Expression of CXCL16 has been reported in atherosclerosis-prone vessels from apolipoprotein-E-deficient (ApoE Ϫ/Ϫ ) mice 23 and human atherosclerotic plaques. 24 Absence of CXCL16 has been shown to accelerate atherosclerosis, enhance macrophage recruitment, and elevate mRNA levels for...

show abstract

“…The transfected human SR-PSOX gene directs expression of a 30 kDa protein that can bind 125 I-OxLDL with a similar affinity to that of other scavenger receptors. Two years after the original identification of SR-PSOX, it was shown to be identical to an unusual membrane-bound CXC chemokine called CXCL16 (96,97). Recent reports have shown that SR-PSOX/CXCL16 mediates the binding and phagocytosis of Gram-negative and Gram-positive bacteria and that this binding activity maps to the chemokine domain, which is also responsible for the recognition of OxLDL (98,99).…”

Section: Sr-psox (Cxcl16)mentioning

confidence: 99%

Thematic review series: The Immune System and Atherogenesis. Recent insights into the biology of macrophage scavenger receptors

Greaves

Gordon

2005

Journal of Lipid Research

188

115

View full text Add to dashboard Cite

Scavenger receptors were originally defined by their ability to bind and internalize modified lipoproteins. Macrophages express at least six structurally different cell surface receptors for modified forms of LDL that contribute to foam cell formation in atherosclerosis. In addition to their role in the pathology of atherosclerosis, macrophage scavenger receptors, especially SR-A, play critical roles in innate immunity, apoptotic cell clearance, and tissue homeostasis. In this review, we highlight recent advances in understanding the biology of macrophage scavenger receptors as pattern recognition receptors for both infectious nonself (pathogens) and modified self (apoptotic cells and modified LDL). We critically evaluate the potential of scavenger receptors and their ligands as targets for therapeutic intervention in human disease. -Greaves, D. R., and S. Gordon. MACROPHAGE-DERIVED FOAM CELLSFatty streaks, which are the earliest forms of atherosclerotic lesion visible in the artery wall, consist almost entirely of macrophage-derived foam cells (1-3). Monocytes that have been recruited to the subendothelial space at sites of endothelial cell activation differentiate into macrophages and express a range of scavenger receptors, which mediate the endocytic uptake of modified forms of LDL (4). Brown, Goldstein, and colleagues (5, 6) coined the term "scavenger receptor" to distinguish the uptake of modified LDL by macrophages from LDL uptake via the classical LDL receptor, which is feedback inhibited by the accumulation of cholesterol within the cell. Molecular cloning and biochemical characterization of the cellular receptors that mediate the uptake of modified forms of LDL have revealed an unexpectedly large number of endocytic receptors (7, 8). These membrane proteins have widely different structures, and all the scavenger receptors characterized to date bind a number of ligands of biological importance other than modified LDL. Even more puzzling is the recently described scavenger receptor SR-PSOX (scavenger receptor that binds phosphatidylserine and oxidized lipoprotein), which can act both as a receptor [for oxidized LDL (OxLDL)] and as a ligand (the membranebound CXC chemokine, CXCL16).Their lack of feedback inhibition by intracellular cholesterol has made macrophage scavenger receptors scapegoats for the development of macrophage foam cell formation in the artery wall, but it is important to recognize that other metabolic pathways play an important role in the development of cholesteryl ester deposits in macrophage foam cells. Modified apolipoprotein B (apoB)-containing lipoproteins taken up via scavenger receptors are delivered to lysosomes and hydrolyzed to release free cholesterol and fatty acids. The conversion of free cholesterol into cholesteryl esters in macrophages is catalyzed by the enzyme ACAT, and free cholesterol can be converted by the mitochondrial enzyme Cyp27 into 27-hydroxycholesterol, one of several oxysterols that activate changes in macrophage foam cell transcription via the nuc...

show abstract

Expression of the Novel Scavenger Receptor SR-PSOX in Cultured Aortic Smooth Muscle Cells and Umbilical Endothelial Cells

Cited by 60 publications

References 19 publications

Pathogenic role of the CXCL16–CXCR6 pathway in rheumatoid arthritis

Pathogenic role of the CXCL16–CXCR6 pathway in rheumatoid arthritis

CXCR6 Promotes Atherosclerosis by Supporting T-Cell Homing, Interferon-γ Production, and Macrophage Accumulation in the Aortic Wall

Thematic review series: The Immune System and Atherogenesis. Recent insights into the biology of macrophage scavenger receptors

Contact Info

Product

Resources

About