CXCR3 expression and activation of eosinophils: role of IFN-gamma-inducible protein-10 and monokine induced by IFN-gamma.

Abstract

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.

• Authors: T Jinquan, C Jing, H H Jacobi, C M Reimert, A Millner, S Quan, J B Hansen, S Dissing, H J Malling, P S Skov, L K Poulsen
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 165 Issue 3 Pg. 1548-56 (Aug 01 2000) ISSN: 0022-1767 [Print] United States
• PMID: 10903763 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Blood Proteins
• CXCL9 protein, human
• CXCR3 protein, human
• Chemokine CXCL10
• Chemokine CXCL9
• Chemokines, CXC
• Eosinophil Granule Proteins
• IP10-Mig receptor
• Inflammation Mediators
• Intercellular Signaling Peptides and Proteins
• Interleukin-2
• Ligands
• Receptors, CXCR3
• Receptors, Chemokine
• Receptors, Cytokine
• Interleukin-10
• Interferon-gamma
• Ribonucleases
• Calcium

Topics

• Blood Proteins (metabolism)
• Calcium (metabolism)
• Chemokine CXCL10
• Chemokine CXCL9
• Chemokines, CXC (metabolism, physiology)
• Chemotaxis, Leukocyte (immunology)
• Eosinophil Granule Proteins
• Eosinophils (immunology, metabolism)
• Humans
• Inflammation Mediators (physiology)
• Intercellular Signaling Peptides and Proteins
• Interferon-gamma (pharmacology)
• Interleukin-10 (physiology)
• Interleukin-2 (physiology)
• Intracellular Fluid (metabolism)
• Ligands
• Receptors, CXCR3
• Receptors, Chemokine (biosynthesis, physiology)
• Receptors, Cytokine (physiology)
• Ribonucleases
• Signal Transduction (immunology)