CXCR3 expression and activation of eosinophils: role of IFN-gamma-inducible protein-10 and monokine induced by IFN-gamma
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CXC chemokine receptor 3 (CXCR3), predominately expressed on memory/activated T lymphocytes, is a receptor for both IFN-gamma-inducible protein-10 (gamma IP-10) and monokine induced by IFN-gamma (Mig). We report a novel finding that CXCR3 is also expressed on eosinophils. gamma IP-10 and Mig induce eosinophil chemotaxis via CXCR3, as documented by the fact that anti-CXCR3 mAb blocks gamma IP-10- and Mig-induced eosinophil chemotaxis. gamma IP-10- and Mig-induced eosinophil chemotaxis are up- and down-regulated by IL-2 and IL-10, respectively. Correspondingly, CXCR3 protein and mRNA expressions in eosinophils are up- and down-regulated by IL-2 and IL-10, respectively, as detected using flow cytometry, immunocytochemical assay, and a real-time quantitative RT-PCR technique. gamma IP-10 and Mig act eosinophils to induce chemotaxis via the cAMP-dependent protein kinase A signaling pathways. The fact that gamma IP-10 and Mig induce an increase in intracellular calcium in eosinophils confirms that CXCR3 exists on eosinophils. Besides induction to chemotaxis, gamma IP-10 and Mig also activate eosinophils to eosinophil cationic protein release. These results indicate that CXCR3-gamma IP-10 and -Mig receptor-ligand pairs as well as the effects of IL-2 and IL-10 on them may be especially important in the cytokine/chemokine environment for the pathophysiologic events of allergic inflammation, including initiation, progression, and termination in the processes.
Original language | English |
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Journal | Journal of immunology (Baltimore, Md. : 1950) |
Volume | 165 |
Issue number | 3 |
Pages (from-to) | 1548-56 |
Number of pages | 9 |
ISSN | 0022-1767 |
Publication status | Published - 1 Aug 2000 |
- Blood Proteins, Calcium, Chemokine CXCL10, Chemokine CXCL9, Chemokines, CXC, Chemotaxis, Leukocyte, Eosinophil Granule Proteins, Eosinophils, Humans, Inflammation Mediators, Intercellular Signaling Peptides and Proteins, Interferon-gamma, Interleukin-10, Interleukin-2, Intracellular Fluid, Ligands, Receptors, CXCR3, Receptors, Chemokine, Receptors, Cytokine, Ribonucleases, Signal Transduction, Journal Article, Research Support, Non-U.S. Gov't
Research areas
ID: 169715932