CXCL16 is a novel scavenger receptor on platelets and is associated with acute coronary syndrome

Seizer, Peter; Stellos, Konstantinos; Selhorst, Gerhard; Kramer, Benedikt; Lang, Michael; Gawaz, Meinrad; May, Andreas E.

doi:10.1160/th10-10-0689

Cited by 25 publications

(3 citation statements)

References 14 publications

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“…Both CXCR6 and CXCL16 are expressed by platelets and transduce PI3K/Akt signaling leading to platelet activation and adhesion under high shear stress (Borst et al, 2012). CXCL16 is upregulated upon platelet activation and in acute coronary syndrome (Seizer et al, 2011). Cell and platelet-specific models have not been used so far.…”

Section: Chemokines and Soluble Immune Mediatorsmentioning

confidence: 99%

Platelets and their chemokines in atherosclerosisâ€”clinical applications

2014

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The concept of platelets as important players in the process of atherogenesis has become increasingly accepted due to accumulating experimental and clinical evidence. Despite the progress in understanding the molecular details of atherosclerosis, particularly by using animal models, the inflammatory and thrombotic roles of activated platelet s especially in the human system remain difficult to dissect, as often only the complications of atherosclerosis, i.e., stroke and myocardial infarction are definable but not the plaque burden. Platelet indices including platelet count and mean platelet volume (MPV) and soluble mediators released by activated platelets are associated with atherosclerosis. The chemokine CXCL4 has multiple atherogenic activities, e.g., altering the differentiation of T cells and macrophages by inhibiting neutrophil and monocyte apoptosis and by increasing the uptake of oxLDL and synergizing with CCL5. CCL5 is released and deposited on endothelium by activated platelets thereby triggering atherogenic monocyte recruitment, which can be attenuated by blocking the corresponding chemokine receptor CCR5. Atheroprotective and plaque stabilizing properties are attributed to CXCL12, which plays an important role in regenerative processes by attracting progenitor cells. Its release from luminal attached platelets accelerates endothelial healing after injury. Platelet surface molecules GPIIb/IIIa, GP1bα, P-selectin, JAM-A and the CD40/CD40L dyade are crucially involved in the interaction with endothelial cells, leukocytes and matrix molecules affecting atherogenesis. Beyond the effects on the arterial inflammatory infiltrate, platelets affect cholesterol metabolism by binding, modifying and endocytosing LDL particles via their scavenger receptors and contribute to the formation of lipid laden macrophages. Current medical therapies for the prevention of atherosclerotic therapies enable the elucidation of mechanisms linking platelets to inflammation and atherosclerosis.

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Section: Chemokines and Soluble Immune Mediatorsmentioning

confidence: 99%

Platelets and their chemokines in atherosclerosisâ€”clinical applications

2014

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“…In addition to different types of cells such as T cells, macrophages, cytokine-induced smooth muscle cells, and endothelial cells, CXCL16/SR-PSOX has been recently identified for the first time in platelets (Seizer et al, 2011). This protein constitutes an atypical chemokine because it is expressed as a cell surface bound molecule but is also found in a soluble form after shedding.…”

Section: Chemokines In Leukocyte Trafficking and Inflammatory Diseasesmentioning

confidence: 99%

Touch of Chemokines

Blanchet¹,

Langer²,

Weber³

et al. 2012

Front. Immun.

106

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Chemoattractant cytokines or chemokines constitute a family of structurally related proteins found in vertebrates, bacteria, or viruses. So far, 48 chemokine genes have been identified in humans, which bind to around 20 chemokine receptors. These receptors belong to the seven transmembrane G-protein-coupled receptor family. Chemokines and their receptors were originally studied for their role in cellular trafficking of leukocytes during inflammation and immune surveillance. It is now known that they exert different functions under physiological conditions such as homeostasis, development, tissue repair, and angiogenesis but also under pathological disorders including tumorigenesis, cancer metastasis, inflammatory, and autoimmune diseases. Physicochemical properties of chemokines and chemokine receptors confer the ability to homo- and hetero-oligomerize. Many efforts are currently performed in establishing new therapeutically compounds able to target the chemokine/chemokine receptor system. In this review, we are interested in the role of chemokines in inflammatory disease and leukocyte trafficking with a focus on vascular inflammatory diseases, the operating synergism, and the emerging therapeutic approaches of chemokines.

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“…As a transmembrane molecule, CXCL16 (also known as SR-PSOX ) acts as a scavenger receptor for oxidized low-density lipoprotein (oxLDL) uptake, suggesting the involvement of CXCL16 in lipid metabolism [ 6 ]. While in a soluble form, CXCL16 has been found to interact with its receptor, CXCR6, and thus functions as an attractant and adhesion molecule for CXCR6-expressing T cells, which contribute to the development of atherosclerosis [ 7 , 8 ]. Mounting evidences have uncovered the close association of CXCL16 with the development of diverse human inflammatory diseases, including atherosclerosis [ 9 ], coronary artery disease [ 10 ], and MI [ 11 ].…”

Section: Introductionmentioning

confidence: 99%

The Impact of tagSNPs in CXCL16 Gene on the Risk of Myocardial Infarction in a Chinese Han Population

Cheng

Cai

et al. 2017

Disease Markers

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CXCL16 has been demonstrated to be involved in the development of atherosclerosis and myocardial infarction (MI). Nonetheless, the role of the CXCL16 polymorphisms on MI pathogenesis is far to be elucidated. We herein genotyped four tagSNPs in CXCL16 gene (rs2304973, rs1050998, rs3744700, and rs8123) in 275 MI patients and 670 control subjects, aimed at probing into the impact of CXCL16 polymorphisms on individual susceptibility to MI. Multivariate logistic regression analysis showed that C allele (OR = 1.31, 95% CI = 1.03–1.66, and P = 0.029) and CC genotype (OR = 1.84, 95% CI = 1.11–3.06, and P = 0.018) of rs1050998 were associated with increased MI risk; and C allele (OR = 0.77, 95% CI = 0.60–0.98, and P = 0.036) of rs8123 exhibited decreased MI risk, while the other two tagSNPs had no significant effect. Consistently, the haplotype rs2304973T-rs1050998C-rs3744700G-rs8123A containing the C allele of rs1050998 and A allele of rs8123 exhibited elevated MI risk (OR = 1.41, 95% CI = 1.02–1.96, and P = 0.037). Further stratified analysis unveiled a more apparent association with MI risk among younger subjects (≤60 years old). Taken together, our results provided the first evidence that CXCL16 polymorphisms significantly impacted MI risk in Chinese subjects.

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CXCL16 is a novel scavenger receptor on platelets and is associated with acute coronary syndrome

Cited by 25 publications

References 14 publications

Platelets and their chemokines in atherosclerosisâ€”clinical applications

Platelets and their chemokines in atherosclerosisâ€”clinical applications

Touch of Chemokines

The Impact of tagSNPs in CXCL16 Gene on the Risk of Myocardial Infarction in a Chinese Han Population

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