NDLI: Chemerin contributes to inflammation by promoting macrophage adhesion to VCAM-1 and fibronectin through clustering of VLA-4 and VLA-5.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Hart, Rosie Greaves, David R.
Description	Country affiliation: United kingdom Author Affiliation: Hart R ( Sir William Dunn School of Pathology, University of Oxford, Oxford, United Kingdom.)
Abstract	Chemerin is a potent macrophage chemoattractant protein. We used murine peritoneal exudate cells (PECs) in adhesion, flow cytometry, and confocal microscopy assays to test the hypothesis that chemerin can also contribute to inflammation by promoting macrophage adhesion. Chemerin stimulated the adhesion of PECs to the extracellular matrix protein fibronectin and to the adhesion molecule VCAM-1 within a minute, with an EC(50) of 322 and 196 pM, respectively. Experiments using pertussis toxin and PECs from ChemR23(-/-) mice demonstrated that chemerin stimulated the adhesion of macrophages via the Gi protein-coupled receptor ChemR23. Blocking Abs against integrin subunits revealed that 89% of chemerin-stimulated adhesion to fibronectin was dependent on increased avidity of the integrin VLA-5 (alpha(5)beta(1)) and that 88% of adhesion to VCAM-1 was dependent on increased avidity of VLA-4 (alpha(4)beta(1)). Although chemerin was unable to induce an increase in integrin affinity as judged by the binding of soluble ligand, experiments using confocal microscopy revealed an increase in valency resulting from integrin clustering as the mechanism responsible for chemerin-stimulated macrophage adhesion. PI3K, Akt, and p38 were identified as key signaling mediators in chemerin-stimulated adhesion. The finding that chemerin can rapidly stimulate macrophage adhesion to extracellular matrix proteins and adhesion molecules, taken together with its ability to promote chemotaxis, suggests a novel role for chemerin in the recruitment and retention of macrophages at sites of inflammation.
ISSN	00221767
e-ISSN	15506606
Journal	The Journal of Immunology
Issue Number	6
Volume Number	185
Language	English
Publisher	The American Association of Immunologists
Publisher Date	2010-09-15
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Chemotactic Factors Physiology Fibronectins Metabolism Inflammation Mediators Integrin Alpha4beta1 Integrin Alpha5beta1 Intercellular Signaling Peptides And Proteins Macrophages, Peritoneal Immunology Receptor Aggregation Vascular Cell Adhesion Molecule-1 Animals Cell Adhesion Cell Line Chemokines Chemotaxis, Leukocyte Extracellular Matrix Pathology Mice Mice, Inbred C57bl Mice, Knockout Protein Binding Receptors, G-protein-coupled Deficiency Genetics Research Support, Non-u.s. Gov't Discipline Immunology
Content Type	Text
Resource Type	Article
Subject	Immunology and Allergy Immunology

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