Chemerin Contributes to Inflammation by Promoting Macrophage Adhesion to VCAM-1 and Fibronectin through Clustering of VLA-4 and VLA-5

Hart, Rosie; Greaves, David R.

doi:10.4049/jimmunol.0902154

Cited by 151 publications

(125 citation statements)

References 63 publications

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“…This experimental approach revealed that chemerin was as effective as CCL3, a reference chemokine, in inducing DC arrest on coated glass capillary surfaces, and similar results were obtained using flow chambers coated with RA-activated endothelial cells. Taken together, these two experimental approaches indicate that chemerin, in addition to the previously documented ability to induce b 1 integrin clustering (13), can also promote in DC the high-affinity conformational state of b 1 integrin and induce VCAM-1-dependent cell arrest.…”

Section: Discussionmentioning

confidence: 87%

“…Many tissues express chemerin in a constitutive manner, although the nature of the producing cells is still largely unknown (6). ChemR23, the functional chemerin receptor (also known as CMKLR1 in humans and Dez in the mouse), is a G protein-coupled receptor expressed in various leukocyte populations, including mDC, pDC, monocytes, macrophages, and NK cells (9)(10)(11)(12)(13). More recently, two other high-affinity chemerin receptors were described, as follows: GPR1, a poor signaling receptor mainly expressed in the CNS, and CCRL2/ACKR5, a member of the atypical chemokine receptor family (also known as LCCR in the mouse) (8,14).…”

mentioning

confidence: 99%

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Endothelial Cell–Derived Chemerin Promotes Dendritic Cell Transmigration

Gonzalvo-Feo

Prete

Pruenster

et al. 2014

The Journal of Immunology

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ChemR23 is a chemotactic receptor expressed by APCs, such as dendritic cells, macrophages, and NK cells. Chemerin, the ChemR23 ligand, was detected by immunohistochemistry, to be associated with inflamed endothelial cells in autoimmune diseases, such as lupus erythematosus, psoriasis, and rheumatoid arthritis. This study reports that blood and lymphatic murine endothelial cells produce chemerin following retinoic acid stimulation. Conversely, proinflammatory cytokines, such as TNF-α, IFN-γ, and LPS, or calcitriol, are not effective. Retinoic acid–stimulated endothelial cells promoted dendritic cell adhesion under shear stress conditions and transmigration in a ChemR23-dependent manner. Activated endothelial cells upregulated the expression of the atypical chemotactic receptor CCRL2/ACKR5, a nonsignaling receptor able to bind and present chemerin to ChemR23+ dendritic cells. Accordingly, activated endothelial cells expressed chemerin on the plasma membrane and promoted in a more efficient manner chemerin-dependent transmigration of dendritic cells. Finally, chemerin stimulation of myeloid dendritic cells induced the high-affinity binding of VCAM-1/CD106 Fc chimeric protein and promoted VCAM-1–dependent arrest to immobilized ligands under shear stress conditions. In conclusion, this study reports that retinoic acid–activated endothelial cells can promote myeloid and plasmacytoid dendritic cell transmigration across endothelial cell monolayers through the endogenous production of chemerin, the upregulation of CCRL2, and the activation of dendritic cell β1 integrin affinity.

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Section: Discussionmentioning

confidence: 87%

mentioning

confidence: 99%

Endothelial Cell–Derived Chemerin Promotes Dendritic Cell Transmigration

Gonzalvo-Feo

Prete

Pruenster

et al. 2014

The Journal of Immunology

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“…The regulation of ChemR23 expression was previously studied in mouse macrophages, where ChemR23 was downregulated by inflammatory stimuli such as TLR ligands (LPS, CpG) and inflammatory cytokines, and upregulated by TGF-b (18,38). The authors of these studies concluded that ChemR23 has a role in naive and anti-inflammatory macrophages only.…”

Section: Discussionmentioning

confidence: 96%

“…It binds two ligands: the peptide chemerin (12) and the eicosapentaenoic acid-derived lipid mediator 5S,12R,18R-trihydroxy-6Z,8E,10E,14Z,16E-eicosapentaenoic acid named resolvin E1 (RvE1) (13,14). Chemerin is present in high amounts in inflammatory fluids (15), has antimicrobial activities (16), was shown to attract ChemR23-expressing leukocytes (12,17), and promotes adhesion of macrophages to extracellular matrix proteins (18). In addition, chemerin was recently discovered to be an adipokine (10).…”

mentioning

confidence: 99%

ChemR23, the Receptor for Chemerin and Resolvin E1, Is Expressed and Functional on M1 but Not on M2 Macrophages

Herová

Schmid

Gemperle

et al. 2015

The Journal of Immunology

139

100

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ChemR23 is a G protein–coupled receptor that is triggered by two ligands, the peptide chemerin and the eicosapentaenoic acid–derived lipid mediator resolvin E1 (RvE1). Chemerin acts as a chemoattractant for monocytes and macrophages, whereas RvE1 promotes resolution of inflammation-inducing macrophage phagocytosis of apoptotic neutrophils. Although ChemR23-mediated signaling plays a role in mononuclear cell migration to inflamed tissue, as well as in the resolution of inflammation, its regulation in different polarization states of macrophages is largely unknown. We analyzed the expression and function of ChemR23 in monocytes and differently activated human primary macrophages. Using 5′ RACE, we identified three transcription start sites and several splice variants of ChemR23 in both monocytes and macrophages. Although the promoters P1 and P3 are used equally in unpolarized macrophages, stimulation with LPS or IFN-γ leads to increased transcription from P3 in inflammatory M1 macrophages. Such ChemR23-expressing M1 macrophages are chemotactic to chemerin, whereas M2 macrophages not expressing ChemR23 surface receptor are not. Repolarization of ChemR23-expressing M1 macrophages with 10 nM RvE1 increases IL-10 transcription and phagocytosis of microbial particles, leading to a resolution-type macrophage distinct from the M2 phenotype. These results show that ChemR23 is tightly regulated in response to inflammatory and anti-inflammatory stimuli. The restricted expression of ChemR23 in naive and M1 macrophages supports the role of ChemR23 in the attraction of macrophages to inflamed tissue by chemerin and in the initiation of resolution of inflammation through RvE1-mediated repolarization of human M1 macrophages toward resolution-type macrophages.

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“…Spiroglou and colleagues found a significant correlation between coronary atherosclerosis and epicardial chemerin levels [Spiroglou et al 2010]. Hart and Greaves reported a contribution of chemerin in the progression of atherosclerosis by stimulating adhesion of macrophages to the extracellular matrix protein fibronectin and vascular cell adhesion molecule-1 (VCAM-1) [Hart and Greaves, 2010]. In addition, the chemerin molecule was shown to activate endopeptidases MMP-2 and MMP-9 belonging to matrix metalloproteinases that play a key role in plaque instability [Kaur et al 2010], increase the expressions of adhesion molecules such as E-selectin and ICAM-1 [Landgraf et al 2012], and was considered a new biomarker for coronary atherosclerosis.…”

Section: Chemerin and Cardiovascular Diseasesmentioning

confidence: 99%

Chemerin as an independent predictor of cardiovascular event risk

İnci

Aksan

Doğan

2016

Therapeutic Advances in Endocrinology

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Currently, coronary artery disease (CAD) is considered a major ailment in humans with widespread prevalence. CAD also accounts for high mortality rates around the world that involves several known risk factors. Chemerin is a novel adipokinine that is associated with inflammation and adipogenesis. Furthermore, experimental and clinical data indicate that localized as well as circulating chemerin expression and activation are elevated in numerous metabolic and inflammatory diseases including psoriasis, obesity, type 2 diabetes, metabolic syndrome and cardiovascular disease. Chemerin is accepted as being a strong marker because the serum chemerin levels are increased in a CAD condition. However, the chimeric characteristics of chemerin have not been fully investigated. Although chemerin is known to be responsible for CAD development among other factors, authors still investigate it at the marker level. This review focuses on chemerin expression, processing, biological function and relevance to human diseases, and on the role of chemerin in the maintenance of a cardiovascular disease.

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Chemerin Contributes to Inflammation by Promoting Macrophage Adhesion to VCAM-1 and Fibronectin through Clustering of VLA-4 and VLA-5

Abstract: Material

Cited by 151 publications

References 63 publications

Endothelial Cell–Derived Chemerin Promotes Dendritic Cell Transmigration

Endothelial Cell–Derived Chemerin Promotes Dendritic Cell Transmigration

ChemR23, the Receptor for Chemerin and Resolvin E1, Is Expressed and Functional on M1 but Not on M2 Macrophages

Chemerin as an independent predictor of cardiovascular event risk

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