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 EC50 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. The Journal of Immunology, 2010, 185: 3728-3739.
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Chiba Univ, Grad Sch Med, Dept Clin Cell Biol, Chuo Ku, Chiba 2608670, Japan
Chiba Univ, Grad Sch Med, Dept Mol & Tumor Pathol, Chuo Ku, Chiba 2608670, JapanChiba Univ, Grad Sch Med, Dept Clin Cell Biol, Chuo Ku, Chiba 2608670, Japan
Harima, Akane
Nakaseko, Chiaki
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Chiba Univ, Grad Sch Med, Dept Clin Cell Biol, Chuo Ku, Chiba 2608670, JapanChiba Univ, Grad Sch Med, Dept Clin Cell Biol, Chuo Ku, Chiba 2608670, Japan
Nakaseko, Chiaki
Yokota, Akira
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Chiba Univ, Grad Sch Med, Dept Clin Cell Biol, Chuo Ku, Chiba 2608670, Japan
Chiba Univ, Grad Sch Med, Dept Mol & Tumor Pathol, Chuo Ku, Chiba 2608670, JapanChiba Univ, Grad Sch Med, Dept Clin Cell Biol, Chuo Ku, Chiba 2608670, Japan
Yokota, Akira
Kitagawa, Motoo
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Chiba Univ, Grad Sch Med, Dept Mol & Tumor Pathol, Chuo Ku, Chiba 2608670, JapanChiba Univ, Grad Sch Med, Dept Clin Cell Biol, Chuo Ku, Chiba 2608670, Japan
Kitagawa, Motoo
Morimoto, Chikao
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Univ Tokyo, Inst Med Sci, Div Clin Immunol, Minato Ku, Tokyo 1088639, JapanChiba Univ, Grad Sch Med, Dept Clin Cell Biol, Chuo Ku, Chiba 2608670, Japan
Morimoto, Chikao
Harigaya, Kenichi
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Chiba Univ, Grad Sch Med, Dept Mol & Tumor Pathol, Chuo Ku, Chiba 2608670, JapanChiba Univ, Grad Sch Med, Dept Clin Cell Biol, Chuo Ku, Chiba 2608670, Japan
Harigaya, Kenichi
Saito, Yasushi
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Chiba Univ, Grad Sch Med, Dept Clin Cell Biol, Chuo Ku, Chiba 2608670, JapanChiba Univ, Grad Sch Med, Dept Clin Cell Biol, Chuo Ku, Chiba 2608670, Japan