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PMID:10903763

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Citation

Jinquan, T, Jing, C, Jacobi, HH, Reimert, CM, Millner, A, Quan, S, Hansen, JB, Dissing, S, Malling, HJ, Skov, PS and Poulsen, LK (2000) CXCR3 expression and activation of eosinophils: role of IFN-gamma-inducible protein-10 and monokine induced by IFN-gamma. J. Immunol. 165:1548-56

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.

Links

PubMed

Keywords

Blood Proteins/secretion; Calcium/metabolism; Chemokine CXCL10; Chemokine CXCL9; Chemokines, CXC/metabolism; Chemokines, CXC/physiology; Chemotaxis, Leukocyte/immunology; Eosinophil Granule Proteins; Eosinophils/immunology; Eosinophils/metabolism; Eosinophils/secretion; 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; Receptors, Chemokine/physiology; Receptors, Cytokine/physiology; Ribonucleases; Signal Transduction/immunology

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

HUMAN:CXCL9

enables

GO:0008009: chemokine activity

ECO:0000304: author statement supported by traceable reference used in manual assertion

F

Seeded From UniProt

complete

HUMAN:CXCL9

involved_in

GO:0007186: G protein-coupled receptor signaling pathway

ECO:0000304: author statement supported by traceable reference used in manual assertion

P

Seeded From UniProt

complete

HUMAN:CXCL9

involved_in

GO:0006954: inflammatory response

ECO:0000304: author statement supported by traceable reference used in manual assertion

P

Seeded From UniProt

complete

HUMAN:CXCL9

involved_in

GO:0006935: chemotaxis

ECO:0000304: author statement supported by traceable reference used in manual assertion

P

Seeded From UniProt

complete

HUMAN:CXL10

enables

GO:0008009: chemokine activity

ECO:0000304: author statement supported by traceable reference used in manual assertion

F

Seeded From UniProt

complete

HUMAN:CXL10

enables

GO:0008603: cAMP-dependent protein kinase regulator activity

ECO:0000304: author statement supported by traceable reference used in manual assertion

F

Seeded From UniProt

complete

HUMAN:CXL10

involved_in

GO:0006935: chemotaxis

ECO:0000304: author statement supported by traceable reference used in manual assertion

P

Seeded From UniProt

complete

HUMAN:CXL10

involved_in

GO:0006954: inflammatory response

ECO:0000304: author statement supported by traceable reference used in manual assertion

P

Seeded From UniProt

complete

HUMAN:CXL10

involved_in

GO:0007166: cell surface receptor signaling pathway

ECO:0000304: author statement supported by traceable reference used in manual assertion

P

Seeded From UniProt

complete

HUMAN:CXCR3

involved_in

GO:0006935: chemotaxis

ECO:0000304: author statement supported by traceable reference used in manual assertion

P

Seeded From UniProt

complete


See also

References

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