Identification of chemerin receptor (ChemR23) in human endothelial cells: Chemerin-induced endothelial angiogenesis

Kaur, Jasbinder; Adya, Raghu; Tan, Bee K.; Chen, Jing; Randeva, Harpal S.

doi:10.1016/j.bbrc.2009.12.150

Cited by 292 publications

(286 citation statements)

References 27 publications

Supporting

Mentioning

268

Contrasting

Unclassified

Order By: Relevance

“…Differences in the experimental setup may well account for the not fully congruent results between the in vivo mouse studies and our in vitro human studies. Although multiple cell types are affected after systemic application of RvE1 in mice, including endothelial cells expressing ChemR23 (11,14) and neutrophils expressing the BLT1 receptor (36), these additional stimuli are lacking in our in vitro study on primary human macrophages.…”

Section: Discussionmentioning

confidence: 99%

“…ChemR23, also known as the Chemokine-like Receptor 1, is a G protein-coupled receptor expressed on monocytes and macrophages, dendritic cells (8), and NK cells (9), as well as on adipocytes (10) and endothelial cells (11). 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).…”

mentioning

confidence: 99%

See 1 more Smart Citation

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

133

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionmentioning

confidence: 99%

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

133

View full text Add to dashboard Cite

show abstract

“…K d and B max values were calculated by nonlinear regression (Prism software; GraphPad) using as total and nonspecific binding the MCF obtained with ChemR23-expressing and WT CHO cells, respectively. For competition-binding experiments, 100,000 ChemR23-expressing CHO cells were incubated for 1 h at 4˚C in 100 ml cold FACS buffer containing 10 …”

Section: Nanobody-binding Assaysmentioning

confidence: 99%

“…ChemR23 is expressed by various leukocyte populations, including monocytes, macrophages, myeloid and plasmacytoid dendritic cells, NK cells, and microglial cells (2)(3)(4). ChemR23 expression was also described in nonleukocyte cell populations, including preadipocytes and adipocytes (5,6), osteoclasts (7), chondrocytes (8), skeletal muscle cells (9), and endothelial cells (10).…”

mentioning

confidence: 99%

Development by Genetic Immunization of Monovalent Antibodies (Nanobodies) Behaving as Antagonists of the Human ChemR23 Receptor

Peyrassol

Laeremans

Gouwy

et al. 2016

The Journal of Immunology

View full text Add to dashboard Cite

The generation of Abs that recognize the native conformation of G protein–coupled receptors can be a challenging task because, like most multimembrane-spanning proteins, they are extremely difficult to purify as native protein. By combining genetic immunization, phage display, and biopanning, we identified two functional monovalent Abs (nanobodies) targeting ChemR23. The two nanobodies (CA4910 and CA5183) were highly specific for the human receptor and bind ChemR23 with moderate affinity. Binding studies also showed that they share a common binding site that overlaps with that of chemerin, the natural ligand of ChemR23. Consistent with these results, we found that the nanobodies were able to antagonize chemerin-induced intracellular calcium increase. The inhibition was partial when chemerin was used as agonist and complete when the chemerin(149-157) nonapeptide was used as agonist. Engineering of a bivalent CA4910 nanobody resulted in a relatively modest increase in affinity but a marked enhancement of efficacy as an antagonist of chemerin induced intracellular calcium mobilization and a much higher potency against the chemerin(149–157) nonapeptide-induced response. We also demonstrated that the fluorescently labeled nanobodies detect ChemR23 on the surface of human primary cell populations as efficiently as a reference mouse mAb and that the bivalent CA4910 nanobody behaves as an efficient antagonist of chemerin-induced chemotaxis of human primary cells. Thus, these nanobodies constitute new tools to study the role of the chemerin/ChemR23 system in physiological and pathological conditions.

show abstract

“…Ainsi, des cytokines inflammatoires pourraient stimuler la production de chémérine par les adipocytes, expliquant en partie les taux plasmatiques élevés observés en cas d'obésité. [11][12][13] (Figure 2). Contrairement à CMKLR1, le récepteur GPR1 n'est pas présent à la surface des cellules immunitaires, mais est exprimé par des cellules du système nerveux central comme les cellules de l'hippocampe, ou encore les cellules U7 (lignée de glioblastome) [14,15].…”

Section: Structure Et Expressionunclassified

La chémérine

2015

View full text Add to dashboard Cite

> La chémérine est une adipocytokine proinflammatoire exprimée et sécrétée majoritairement par les adipocytes. Elle a été initialement impliquée dans la régulation du système immunitaire, de l'adipogenèse et du métabo-lisme énergétique. Cependant, plusieurs études récentes montrent que cette adipocytokine et ses récepteurs sont exprimés au niveau des gonades. In vitro, elle diminue la stéroïdogenèse des cellules ovariennes et testiculaires de rongeurs et d'humains. La chémérine et ses récepteurs sont aussi présents au niveau du placenta. Ils y jouent un rôle important dans la régulation du métabo-lisme foeto-maternel, de la croissance du foetus et de l'homéostasie métabolique pendant la grossesse. < que carboxypeptidase N/B et chymase) libérant différentes isoformes dépourvues chacune de plusieurs acides aminés terminaux [1] comme le décrit la Figure 1. Dans le plasma de l'homme sain, la prochémé-rine représente 80 % de la chémérine totale, alors que dans le liquide synovial de patients atteints d'arthrite, ou dans le liquide céphalo-rachidien de patients atteints de glioblastome, la chémérine 158K est prépondérante [2]. Dans tous les cas, de faibles taux de chémérine S157 ont été retrouvés [2]. Dans la littérature, les concentrations plasmatique et sérique de la chémérine varient entre 3 et 4,4 nM chez l'homme [3, 4] et 0,5 à 0,6 nM chez la souris [5]. L'homologie de séquence primaire de la chémérine humaine avec celle du porc est de 84 %, 79 % avec le bovin, 66 % avec le rat et 63 % avec la souris [6]. La chémérine est exprimée dans plusieurs tissus, principalement le foie, le rein, le pancréas, mais aussi le tissu adipeux brun et blanc d'où sa qualification d'adipocytokine. Elle est aussi présente dans l'hypophyse, le placenta, l'ovaire et le testicule, suggérant son rôle potentiel dans la reproduction. Mode d'action de la chémérineLa chémérine interagit avec les cellules en se fixant sur trois récep-teurs à sept domaines transmembranaires couplés aux protéines G : CMKLR1 (chemokine like receptor 1, aussi connu sous les noms chemR23 ou DEZ), GPR1 (G protein-coupled receptor 1) et CCRL2 (C-C chemokine receptor-like 2, pour revue [7,8]) (Figure 2 Depuis plusieurs années, le tissu adipeux est considéré comme un véritable organe endocrine capable de sécréter des molécules, appelées adipocytokines, impliquées dans la régulation de l'homéostasie éner-gétique. La chémérine est l'une de ces adipocytokines, récemment découverte. Elle joue un rôle important dans le développement de l'inflammation, mais aussi dans l'adipogenèse et la régulation du métabolisme du glucose dans les cellules musculaires squelettiques et les cellules endothéliales. Dans cette synthèse, nous décri-rons brièvement les rôles connus de la chémérine dans le métabolisme et la reproduction, chez la femelle et le mâle, puis son implication potentielle dans le syndrome des ovaires polykystiques (SOPK) chez la femme et son importance dans la physiologie foeto-maternelle. Structure et expressionLa chémérine est une protéine chémoattractante de 163 acid...

show abstract

Identification of chemerin receptor (ChemR23) in human endothelial cells: Chemerin-induced endothelial angiogenesis

Cited by 292 publications

References 27 publications

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

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

Development by Genetic Immunization of Monovalent Antibodies (Nanobodies) Behaving as Antagonists of the Human ChemR23 Receptor

La chémérine

Contact Info

Product

Resources

About