Mouse ChemR23 Is Expressed in Dendritic Cell Subsets and Macrophages, and Mediates an Anti-Inflammatory Activity of Chemerin in a Lung Disease Model
| Autor: | Valérie Wittamer, Patricia de Nadai, Maryse Brait, Jean-Denis Franssen, Benjamin Bondue, Olivier De Henau, François Huaux, Laurie Rouger, Marc Parmentier, Souphalone Luangsay |
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| Rok vydání: | 2009 |
| Předmět: |
Lipopolysaccharides
Chemokine Neutrophils medicine.medical_treatment Immunology Inflammation CMKLR1 Receptors G-Protein-Coupled Mice Aequorin Immune system medicine Animals Immunology and Allergy Chemerin Lung Mice Knockout Chemotactic Factors biology Chemotaxis Macrophages Dendritic Cells Pneumonia Dendritic cell Recombinant Proteins Cell biology Killer Cells Natural Mice Inbred C57BL Disease Models Animal Cytokine Acute Disease Knockout mouse biology.protein Intercellular Signaling Peptides and Proteins Calcium Receptors Chemokine Chemokines medicine.symptom Apoproteins Peptides Bronchoalveolar Lavage Fluid |
| Zdroj: | The Journal of Immunology. 183:6489-6499 |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.0901037 |
| Popis: | Chemerin is the ligand of the ChemR23 receptor and a chemoattractant factor for human immature dendritic cells (DCs), macrophages, and NK cells. In this study, we characterized the mouse chemerin/ChemR23 system in terms of pharmacology, structure-function, distribution, and in vivo biological properties. Mouse chemerin is synthesized as an inactive precursor (prochemerin) requiring, as in human, the precise processing of its C terminus for generating an agonist of ChemR23. Mouse ChemR23 is highly expressed in immature plasmacytoid DCs and at lower levels in myeloid DCs, macrophages, and NK cells. Mouse prochemerin is expressed in most epithelial cells acting as barriers for pathogens but not in leukocytes. Chemerin promotes calcium mobilization and chemotaxis on DCs and macrophages and these functional responses were abrogated in ChemR23 knockout mice. In a mouse model of acute lung inflammation induced by LPS, chemerin displayed potent anti-inflammatory properties, reducing neutrophil infiltration and inflammatory cytokine release in a ChemR23-dependent manner. ChemR23 knockout mice were unresponsive to chemerin and displayed an increased neutrophil infiltrate following LPS challenge. Altogether, the mouse chemerin/ChemR23 system is structurally and functionally conserved between human and mouse, and mouse can therefore be considered as a good model for studying the anti-inflammatory role of this system in the regulation of immune responses and inflammatory diseases. |
| Databáze: | OpenAIRE |
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